IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Farber lipogranulomatosis

1 .Inheritance

Autosomal Recessive

2. Gene Name

ASAH1

3. Protein Name

Acid ceramidase

4. Chromosomal Location

8p22-p21.3

5. Protein Sequence

>sp|Q13510|ASAH1_HUMAN Acid ceramidase OS=Homo sapiens OX=9606 GN=ASAH1 PE=1 SV=5

MPGRSCVALVLLAAAVSCAVAQHAPPWTEDCRKSTYPPSGPTYRGAVPWYTINLDLPPYK

RWHELMLDKAPVLKVIVNSLKNMINTFVPSGKIMQVVDEKLPGLLGNFPGPFEEEMKGIA

AVTDIPLGEIISFNIFYELFTICTSIVAEDKKGHLIHGRNMDFGVFLGWNINNDTWVITE

QLKPLTVNLDFQRNNKTVFKASSFAGYVGMLTGFKPGLFSLTLNERFSINGGYLGILEWI

LGKKDVMWIGFLTRTVLENSTSYEEAKNLLTKTKILAPAYFILGGNQSGEGCVITRDRKE

SLDVYELDAKQGRWYVVQTNYDRWKHPFFLDDRRTPAKMCLNRTSQENISFETMYDVLST

KPVLNKLTVYTTLIDVTKGQFETYLRDCPDPCIGW

6. Gene Sequence

>NC_000008.11:c18084961-18055992 Homo sapiens chromosome 8, GRCh38.p14 Primary Assembly

GAAATCCAACCCGGTCACCTACCCGCGCGACTGTGTCCACGGATGGCACGAAAGCCAAGCGAGTCCCCCT

GCCGAGCTACTCGCGTCCGCCTCCTCCCAAGCTGAGCTCTGCTCCGCCCACCTGAGTCCTTCGCCAGTTA

GGAGGAAACACAGCCGCTTAATGAACTGCTGCATCGGGCTGGGAGAGAAAGCTCGCGGGTCCCACCGGGC

CTCCTACCCAAGTCTCAGCGCGCTTTTCACCGAGGCCTCAATTCTGGGATTTGGCAGCTTTGCTGTGAAA

GCCCAAGTGGGTAACCAACAGCTTGGAGGACCCGAGTGGATTCGATTCTCTCTCACTCCTCGGCCACTCA

ACTGCTCCTTGTCCCTGACTCCGCGGTGGGGATGAATAACTCAACTCATTTCGGGCCGCTTTTCTCAGAG

GGCAAAGATGGGTCAGGGTGGGATGTTACATTAGTGTTGAGACTCTTTGGATCCGTTTCGTGGGTACCGA

GGACGCCTGGGTACGCGGGACAGGCTGCACCCGCCTGCTAGAGGCGCCCCATCGAGGCGCCACGGGTGAA

GCTCCCGGCCCCACCTACGGGGCGGGGCTCCGGCTCGGTCCGACTATTGCCCGCGGTGGGGGAGGGGGAT

GGATCACGCCACGCGCCAAAGGCGATCGCGACTCTCCTTCTGCAGGTAGCCTGGAAGGCTCTCTCTCTTT

CTCTACGCCACCCTTTTCGTGGCACTGAAAAGCCCCGTCCTCTCCTCCCAGTCCCGCCTCCTCCGAGCGT

TCCCCCTACTGCCTGGAATGGTGCGGTCCCAGGTCGCGGGTCACGCGGCGGAGGGGGCGTGGCCTGCCCC

CGGCCCAGCCGGCTCTTCTTTGCCTCTGCTGGAGTCCGGGGAGTGGCGTTGGCTGCTAGAGCGATGCCGG

GCCGGAGTTGCGTCGCCTTAGTCCTCCTGGCTGCCGCCGTCAGCTGTGCCGTCGCGCAGCACGCGCCGCC

GGTGAGTGAGCTTGAGCCGAGGCGCAGAGAGGGGCGTGCAGGTGCGGGCGCGGATGGAGGCGCAGGTGTG

GCGGCGCGAGCGGGTACAAGGAACACCTCGTGCTGGGCAGCTTCTTTACGGGGGTCTGTGGTTTCGTGCA

CAGGGGTGTGGGTGCAGAGCGGGCTGGCGAACCCCGTCCTCGGTAGATTCGGTGCTACCTGCAACTAGAA

CTCCTTTAAAGGAAATCCTAGTCTCTGCAGGATACCTGGGTGTGATTCGCACATTCTTAGATTTGAGTGA

GTGTACTTGAATAACCAGTTCCAGGCCCTTGCATTTTGAAGTGTTTAAATAAAATGTTCCGGTGGACCTG

TGTGCATTACTCAATCAAGGACAGACTGCCTGATGGTCAGGTGCTTTCTCCCGAAGAAGTTCAGGAGTTC

AGCCCAGGATACTGCAGGGCCGTGGGAAACGCTGAGTGGTCCCAAGCTTGGGCGGTGCGAGCAGCCCAGA

GCAGGCCCCAAAGGGCCCCCTGTGGCCTTTTGCACCCAAGTCATGGGATCGCCTGTCCCGTGGCTCTTTC

CCACGAGCAAGTCACAGGGCTACGGACTTCCTAACTGCAAGAGACAGTGAGGGACGAGCGTGACTCTTTC

ATTTTACAGAAGAGGAAGTAGACCTAGAGTGAGAAAATATTTAGCCAGAGGTTACACTGTTGTTTACTGA

ACATGCGTAACGTCCGAGCCTCTTGACGCCCAGTACTCTTTCATAATTCATTTCTTTATAAAGCAATCAG

ACTGCGTTTGTCTTTGCCAACAGAATCGGATAAGTAGGAACCTGGCGCATCTGGCCTGAGGCTAGATGGT

GATGGTCTTGAATAGTTTAGGTAGGTTATTGAAAGTGGAAGCAAGATGTGCATTGTCTTCTTTTATACCT

GTAAGGAGAAATTCTTTAAAATCATGGTGGGATATGATTTAGCCATTAAAATTGATATAATGTTCAGCAG

ATAAAAGTAGAATCCAGAATAGTATATACAGTTTTTCCTGTAATAGGAAAATACACAGAACATGTATGTG

GACACGATTAAAGGCCTTAAAATAAAATTGCTCCATTGTGGGTAGGGAATTAATTTGCTTGACGGTAGTT

GGTTTTATGGGAATTGGGAGAGACTTTGATACTTTGATACTGTCAGGGCCCTTCATTGAAAGACCACCAG

GAACACACCATAAGCTGAACAAATTGGGTTTAGTGTTCTTTGAGGCAAAGGAGACCACACACCATGAGCG

ACGGACGGTAGGTTATAGAAAAAAACCCATTACAGAATTTGAACTTCGGTTGCATGATTTGGGGTAAGAC

TGAGGAACCGGGCTTTGCTGTAGATAGAATGCTGTTAGAAGGTGGGGCAATTCTGACTGAGTAAAGAAGG

AACAGCCATTCTGTTTAGCACGAGAAGGGGATGTTTGGTGTTTTGTGCGTTGCAGGTGCCCTTGTTTTTG

TCTGTTCTTAGAGAAAATCTTCAAGTGGCATTGCTTTGTCTTGGTGTGTCATGTCTCAGAATAATCTTAT

CCGACGTAGGTATCTGTGGGATTGTTGATGTCCAGGAGGAAAACAGAGCTTACCTGGCTGTGAGTGTCAG

ATCGGCTTGTAATAATATTGAGAGATAGCTGTGGGACTCAGAGCAGTTTCAGGTGTTGGAGGCTGTTTTT

TCTTCTTTCTCAATAGCTTTATTTATTCTAGCAAAAGTATTTTGATAGCTATTTTCAGAAGAAGAATTAA

CAACCTCTCAATGGATATAATAGTTCTTATCTAGAACAGCGATTATCAAAGTCTAGTCTGGCCACTGGTG

TCACTTTGGGAAGCTGTTTTCACAGGTTTTCAATGAAACTGGAAAAATAAGAATGCAAAACTAAAATTAT

TAATTTAGAATGTTAATCTTTACTCTGATTGTATGGACTTCAAGTTTTCATTGTTGCAAACGTGTTCTTA

AAAATAACGGCAGAGGTAGATGTTATGTGCATGGAATTTGTTTTGTTTTAACATCTCCATTTGGCAGAAT

AAAAATTTGGACCCTCCTGTGCCAAGGCCTCATTAATTTTTTTTTACTGGCCTGGAAAATCCTGGGATCC

ATGCACTGAAGGACCTTTAGAACCTTACAGAAGTTTAGTGACTTCATTCTCTGAGAAGAATAAGCAGTTT

TTCAACTGGAGTCATTATATGATAAACTATAGCCTCATGGTAACAAAAGATATTTCAAAAGTACTTTCAA

TAAATATGAATAATGAGAAGCAGCTTTAAATTGGAAACAAGTCATTTGATTTAGAACATCTGTAAGGATT

TTTTGTGTGTTTGTTTTTGAGGCTTTTCACAATATTCCTATGTGAAGGTCCTCCTGAGTTATTCTTCATT

ATTGAATTTTTTAGGAGTCTATTAAGAGATGATGGTGAAGACAGTGGCACAAGAAATGTCTGGAGAGATA

GCGCCAGATGACATCATCCAGGGTTCTGTAGACTCTTATTAAGGATTCAGAAATTTATCCTAAAAAATGG

GAGGATCTGGAACCAGCCAATGGGAGGCCATTAGATGGTTTTAGACAAGATAACATTTTCACTTTAAAAA

GATGAGTCTGGATTGGAGGTCAGCAAGGGTAGATATGAGGAGACTAGTCCAGAAAAGAAAACAGGGTGCG

TTGAAGGATGGTGGCGCCAGGGGTGAGGGAGAGAAGTAGATGTTCTAGAAAAAAATCAGGAGGGCGAATG

AGCTGAAGGAATCGTTGGGTGAGGATGAGGGAGTGAGGTGTCAGCGTGACCTGCACATTGCTGAAGTGCT

TCGCTGGGCGAATGGTGGCATCCGTTCCAGGAAACATGGGGAGGGGAAAGCTTGGGGGCTAAAGAATGAG

GATCGTTTTCATTTGGGGTGTATGTTAAATTTCAGGTGGCAGAGAGGCATCCAGCAGGCCACTCGGACTG

GCACTCAGAAGAGAGACACTGAGAGTCACTGGCATAATGATATTATATTTGAAGCCCTTGGAGCAGATGA

ACTTACCTAGAAATAGGATAGAGAAAGAGAAGAAAAGAGAACTAGGCAAAGGCTAAGTAACTTGCACATG

TATGTGTCAAGAAGAGGAGAAATTGCCAAAGTTAAAACAGGACAGGCCGGGCGCGGTGGCTCATGCCTGT

AATCCCAGCACTTTGGGAGGCCAAGGTGGGCAGATCACGTGAGGTCAGGAGTTTGAGACTAGCCTGGCCA

ACATGGAGAAACCCTGTCTCTACTAAAAATACAAAAATTAGCTGGGCATAGTGGCTCACGCCTGTAGTCC

CAGCTACTCAGGAGGCTGAGGCGGGAGAATTGCTTGAACCTGGGAGGGAGAGGTTGCAGTGAGCCAAGAT

CCTGCCATTGCACTCCAGCCTGGACAATGAGCGAAACTTCGTCACAGAAAACAAAAACAAAAAAATAGGA

GAGTAAGTGGAACAGGAAGCTCAGGGAAGAGACTGGGACAGGTTAACTATGTTGAATATTATTGAGATGT

CAGTGGTATTATGATGTTGGGCAACTGGAGGTCATTGGTCACCTCGACTGGAGCAGTGTTGGGGGCAGAA

AACAGCTTGCGGTAGGCTAAGTGTGATTGGCAGGAAAGGAACTAGAGGGGAGAGATGGCTGCTCTGCGTA

ATAAATCTGACCCACTTCATAAGATGTGCGAAGATGAAACGTAATGGCTTAGTAATTAATTGCCAAAGTA

AACTTGTAAACTCATTTTTATGCATCAGCTTCTCATACTAGTTAACAGCGTATGTCAACATTGTTGACAT

TAGCTATTGAATCAGCTTTAGCAATGATTTTCACGCAGTTGCCAGAAATCTCATAGACCCCATCTGGCCT

AGGAATTTATTGCACTTCATCTGCTTTTCCCTACTTCTCCCAAAGAGGGAACACACAGGTGTAATCCATT

CACTTATTCAACAAATACTGCTTGCCTACTATGTGCCAGACTCCTAAACGCTGGGAATGCGTCAGCCAAT

GAGATAGATGAGGTCCTTCCTCTCATGGAGGGTTTATTCACATTCCTTTGACCTAAATATCAGTAGCTTA

ATAGGATGCCATCCCATCAAAGCCCAGAAGACAAGTGAAAACATTTTCAAGCTCATGTGAATTCTTGTAC

ACGTAGGAAACATGCCTCTTTGTATTCAGTGTTTCTGCTGAGTTGTACATAAGAGGACATTATAGGAAAA

ACTTGTCTGCAAAATAGTTGTTGATGAATTCAAGAATTGAATGAATGAAAAATTGTCTGGCTAGAGTTGT

TTGGCTTCTGGTGGGTATGAAAACTGACATGAGGTATGTAATTTTAGATTATCCTTCATTGTCTCTTTCT

7. Motif

Pfam (5 motifs)

Pfam	Position(Independent E-value)	Description
CBAH	143..384(1.7e-51)	PF02275, Linear amide C-N hydrolases, choloylglycine hydrolase family
NAAA-beta	45..107(8.6e-21)	PF15508, beta subunit of N-acylethanolamine-hydrolyzing acid amidase
AAT	249..381(0.0016)	PF03417, Acyl-coenzyme A:6-aminopenicillanic acid acyl-transferase
DUF502	61..91(0.74)	PF04367, Protein of unknown function (DUF502)
HP_OMP	156..212(0.062)	PF01856, Helicobacter outer membrane protein

8. Evolutionary Relationship

Evolutionary analysis by Maximum Likelihood method

The evolutionary history was inferred by using the Maximum Likelihood method and JTT matrix-based model [1]. The tree with the highest log likelihood (-7766.61) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log likelihood value. The proportion of sites where at least 1 unambiguous base is present in at least 1 sequence for each descendent clade is shown next to each internal node in the tree. This analysis involved 100 amino acid sequences. There were a total of 659 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs137853593	17919233	T238K	ENSG00000104763	ENST00000381733	ENSP00000371152	0.06	2.52	TOLERATED
rs137853593	17919233	T216K	ENSG00000104763	ENST00000314146	ENSP00000326970	0.064	2.61	TOLERATED
rs137853593	17919233	T222K	ENSG00000104763	ENST00000262097	ENSP00000262097	0.065	2.43	TOLERATED
rs137853593	17919233	T197K	ENSG00000104763	ENST00000520781	ENSP00000427751	0.076	2.71	TOLERATED
rs137853593	17919233	T132K	ENSG00000104763	ENST00000417108	ENSP00000394125	0.079	2.64	TOLERATED
rs137853594	17922010	E138V	ENSG00000104763	ENST00000262097	ENSP00000262097	0.001	2.49	DELETERIOUS
rs137853594	17922010	E132V	ENSG00000104763	ENST00000314146	ENSP00000326970	0.001	2.68	DELETERIOUS
rs137853594	17922010	E154V	ENSG00000104763	ENST00000381733	ENSP00000371152	0.001	2.6	DELETERIOUS
rs137853596	17916933	N320D	ENSG00000104763	ENST00000262097	ENSP00000262097	0	2.4	DELETERIOUS
rs137853596	17916933	N314D	ENSG00000104763	ENST00000314146	ENSP00000326970	0	2.59	DELETERIOUS
rs137853596	17916933	N336D	ENSG00000104763	ENST00000381733	ENSP00000371152	0	2.53	DELETERIOUS
rs137853596	17916933	N230D	ENSG00000104763	ENST00000417108	ENSP00000394125	0	2.55	DELETERIOUS
rs137853596	17916933	N295D	ENSG00000104763	ENST00000520781	ENSP00000427751	0	2.62	DELETERIOUS
rs137853597	17919892	L176V	ENSG00000104763	ENST00000314146	ENSP00000326970	0.006	2.64	DELETERIOUS
rs137853597	17919892	L198V	ENSG00000104763	ENST00000381733	ENSP00000371152	0.006	2.53	DELETERIOUS
rs137853597	17919892	L182V	ENSG00000104763	ENST00000262097	ENSP00000262097	0.007	2.4	DELETERIOUS
rs137853597	17919892	L92V	ENSG00000104763	ENST00000417108	ENSP00000394125	0.008	2.61	DELETERIOUS
rs137853597	17919892	L157V	ENSG00000104763	ENST00000520781	ENSP00000427751	0.009	2.73	DELETERIOUS
rs141068211	17919807	M185T	ENSG00000104763	ENST00000520781	ENSP00000427751	0.086	2.64	TOLERATED
rs141068211	17919807	M204T	ENSG00000104763	ENST00000314146	ENSP00000326970	0.096	2.59	TOLERATED
rs141068211	17919807	M226T	ENSG00000104763	ENST00000381733	ENSP00000371152	0.097	2.51	TOLERATED
rs141068211	17919807	M210T	ENSG00000104763	ENST00000262097	ENSP00000262097	0.108	2.39	TOLERATED
rs141068211	17919807	M120T	ENSG00000104763	ENST00000417108	ENSP00000394125	0.116	2.57	TOLERATED
rs145873635	17933050	T58M	ENSG00000104763	ENST00000381733	ENSP00000371152	0.061	2.8	TOLERATED
rs145873635	17933050	T42M	ENSG00000104763	ENST00000262097	ENSP00000262097	0.073	2.7	TOLERATED
rs145873635	17933050	T42M	ENSG00000104763	ENST00000520781	ENSP00000427751	0.073	2.85	TOLERATED
rs145873635	17933050	T58I	ENSG00000104763	ENST00000314146	ENSP00000326970	0.212	2.98	TOLERATED
rs145873635	17933050		ENSG00000104763	ENST00000417108	ENSP00000394125
rs147896487	17942276	R12P	ENSG00000104763	ENST00000314146	ENSP00000326970	0	4.32	DELETERIOUS (WARNING LOW CONFIDENCE)
rs147896487	17942276	R12P	ENSG00000104763	ENST00000381733	ENSP00000371152	0	4.32	DELETERIOUS (WARNING LOW CONFIDENCE)
rs150268016	17919816	Y182F	ENSG00000104763	ENST00000520781	ENSP00000427751	0.083	2.64	TOLERATED
rs150268016	17919816	Y223F	ENSG00000104763	ENST00000381733	ENSP00000371152	0.107	2.51	TOLERATED
rs150268016	17919816	Y201F	ENSG00000104763	ENST00000314146	ENSP00000326970	0.11	2.59	TOLERATED
rs150268016	17919816	Y207F	ENSG00000104763	ENST00000262097	ENSP00000262097	0.125	2.39	TOLERATED
rs150268016	17919816	Y117F	ENSG00000104763	ENST00000417108	ENSP00000394125	0.132	2.57	TOLERATED
rs200455852	17921967	K152K	ENSG00000104763	ENST00000262097	ENSP00000262097	1	2.45	TOLERATED
rs200455852	17921967	K146K	ENSG00000104763	ENST00000314146	ENSP00000326970	1	2.69	TOLERATED
rs200455852	17921967	K168K	ENSG00000104763	ENST00000381733	ENSP00000371152	1	2.62	TOLERATED
rs200455852	17921967	K146N	ENSG00000104763	ENST00000314146	ENSP00000326970	0.588	2.69	TOLERATED
rs200455852	17921967	K168N	ENSG00000104763	ENST00000381733	ENSP00000371152	0.591	2.62	TOLERATED
rs200455852	17921967	K152N	ENSG00000104763	ENST00000262097	ENSP00000262097	0.675	2.45	TOLERATED
rs368345612	17915077	L379P	ENSG00000104763	ENST00000314146	ENSP00000326970	0.004	2.67	DELETERIOUS
rs368345612	17915077	L401P	ENSG00000104763	ENST00000381733	ENSP00000371152	0.004	2.59	DELETERIOUS
rs368345612	17915077	L385P	ENSG00000104763	ENST00000262097	ENSP00000262097	0.005	2.46	DELETERIOUS
rs368345612	17915077	L295P	ENSG00000104763	ENST00000417108	ENSP00000394125	0.005	2.72	DELETERIOUS
rs368345612	17915077	L360P	ENSG00000104763	ENST00000520781	ENSP00000427751	0.005	2.73	DELETERIOUS
rs369707059	17928878	W49*	ENSG00000104763	ENST00000262097	ENSP00000262097
rs369707059	17928878	W72*	ENSG00000104763	ENST00000314146	ENSP00000326970
rs369707059	17928878	W65*	ENSG00000104763	ENST00000381733	ENSP00000371152
rs369707059	17928878	W49*	ENSG00000104763	ENST00000520781	ENSP00000427751
rs369707059	17928878		ENSG00000104763	ENST00000417108	ENSP00000394125
rs371666412	17922013	Y137C	ENSG00000104763	ENST00000262097	ENSP00000262097	0	2.49	DELETERIOUS
rs371666412	17922013	Y131C	ENSG00000104763	ENST00000314146	ENSP00000326970	0	2.68	DELETERIOUS
rs371666412	17922013	Y153C	ENSG00000104763	ENST00000381733	ENSP00000371152	0	2.6	DELETERIOUS

Evolutionary analysis of coding SNPs

SNP Id’s	Amino Acid Change	Probability of deleterious effect	Pdel
rs137853593	T238K	probably damaging	0.81
rs137853593	T216K	probably damaging	0.72
rs137853593	T222K	probably damaging	0.67
rs137853593	T197K	probably damaging	0.85
rs137853593	T132K	probably damaging	0.83
rs137853594	E138V	probably damaging	0.78
rs137853594	E132V	probably damaging	0.76
rs137853594	E154V	probably damaging	0.71
rs137853596	N320D	probably damaging	0.64
rs137853596	N314D	probably damaging	0.86
rs137853596	N336D	probably damaging	0.59
rs137853596	N230D	probably damaging	0.57
rs137853596	N295D	probably damaging	0.57
rs137853597	L176V	probably damaging	0.85
rs137853597	L198V	probably damaging	0.85
rs137853597	L182V	probably damaging	0.85
rs137853597	L92V	probably damaging	0.85
rs137853597	L157V	probably damaging	0.85
rs141068211	M185T	probably damaging	0.85
rs141068211	M204T	probably damaging	0.85
rs141068211	M226T	probably damaging	0.85
rs141068211	M210T	probably damaging	0.85
rs141068211	M120T	probably damaging	0.57
rs145873635	T58M	probably damaging	0.57
rs145873635	T42M	probably damaging	0.85
rs145873635	T42M	probably damaging	0.85
rs145873635	T58I	possibly damaging	0.5
rs147896487	R12P	probably damaging	0.85
rs147896487	R12P	probably damaging	0.85
rs150268016	Y182F	possibly damaging	0.5
rs150268016	Y223F	probability of deleterious effect	0.86
rs150268016	Y201F	probably damaging	0.83
rs150268016	Y207F	probably damaging	0.79
rs150268016	Y117F	probably damaging	0.52
rs200455852	K152K	probably damaging	0.85
rs200455852	K146K	probably damaging	0.83
rs200455852	K168K	probably damaging	0.79
rs200455852	K146N	probably damaging	0.88
rs200455852	K168N	probably damaging	0.55
rs200455852	K152N	probably damaging	0.74
rs368345612	L379P	probably damaging	0.73
rs368345612	L401P	probably damaging	0.84
rs368345612	L385P	probably damaging	0.57
rs368345612	L295P	probably damaging	0.57
rs368345612	L360P	probably damaging	0.85
rs371666412	Y137C	probably damaging	0.85
rs371666412	Y131C	probably damaging	0.85
rs371666412	Y153C	probably damaging	0.85

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs137853593	T238K	-4.67	Deleterious	Damaging
rs137853593	T216K	-4.67	Deleterious	Damaging
rs137853593	T222K	-4.67	Deleterious	Damaging
rs137853593	T197K	-4.64	Deleterious	Damaging
rs137853593	T132K	-4.67	Deleterious	Damaging
rs137853594	E138V	-6.16	Deleterious	Damaging
rs137853594	E132V	-6.12	Deleterious	Damaging
rs137853594	E154V	-6.12	Deleterious	Damaging
rs137853596	N320D	-4.48	Deleterious	Damaging
rs137853596	N314D	-4.48	Deleterious	Damaging
rs137853596	N336D	-4.48	Deleterious	Damaging
rs137853596	N230D	-4.65	Deleterious	Damaging
rs137853596	N295D	-4.48	Deleterious	Damaging
rs137853597	L176V	-3	Deleterious	Damaging
rs137853597	L198V	-3	Deleterious	Damaging
rs137853597	L182V	-3	Deleterious	Damaging
rs137853597	L92V	-2.9	Deleterious	Damaging
rs137853597	L157V	-2.9	Deleterious	Damaging
rs141068211	M185T	-2.78	Deleterious	Tolerated
rs141068211	M204T	-2.82	Deleterious	Tolerated
rs141068211	M226T	-2.82	Deleterious	Tolerated
rs141068211	M210T	-2.82	Deleterious	Tolerated
rs141068211	M120T	-2.82	Deleterious	Tolerated
rs145873635	T58M	-2.24	Neutral	Damaging
rs145873635	T42M	-2.37	Neutral	Tolerated
rs145873635	T42M
rs145873635	T58I	-2.13	Neutral	Damaging
rs147896487	R12P	0	Neutral	Damaging
rs147896487	R12P	0.06	Neutral	Damaging
rs150268016	Y182F	-3.27	Deleterious	Tolerated
rs150268016	Y223F	-3.37	Deleterious	Tolerated
rs150268016	Y201F	-3.37	Deleterious	Tolerated
rs150268016	Y207F	-3.37	Deleterious	Tolerated
rs150268016	Y117F	-3.37	Deleterious	Tolerated
rs200455852	K152K	0	Neutral	Tolerated
rs200455852	K146K	0	Neutral	Tolerated
rs200455852	K168K	0	Neutral	Tolerated
rs200455852	K146N	-0.21	Neutral	Tolerated
rs200455852	K168N	-0.21	Neutral	Tolerated
rs200455852	K152N	-0.21	Neutral	Tolerated
rs368345612	L379P	-4.79	Deleterious	Damaging
rs368345612	L401P	-4.79	Deleterious	Damaging
rs368345612	L385P	-4.79	Deleterious	Damaging
rs368345612	L295P	-5.03	Deleterious	Damaging
rs368345612	L360P	-4.87	Deleterious	Damaging
rs371666412	Y137C	-8.02	Deleterious	Damaging
rs371666412	Y131C	-7.99	Deleterious	Damaging
rs371666412	Y153C	-7.99	Deleterious	Damaging

SNAP2

Wildetype Amino Acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accurancy
T	238	K	Effect	96	98%
T	216	K	Neutral	25	78%
T	222	K	Effect	26	89%
T	197	K	Neutral	34	76%
T	132	K	Effect	26	98%
E	138	V	Neutral	63	78%
E	132	V	Effect	63	85%
N	154	V	Effect	96	55%
N	320	D	Effect	96	55%
N	314	D	Effect	75	45%
N	336	D	Effect	65	65%
N	230	D	Effect	42	98%
N	295	D	Effect	35	65%
L	176	V	Effect	-29	32%
L	198	V	Effect	56	65%
L	182	V	Effect	36	65%
L	92	V	Effect	75	23%
L	157	V	Effect	63	36%
M	185	T	Effect	36	36%
M	204	T	Effect	25	56%
M	226	T	Effect	36	78%
M	210	T	Effect	45	95%
M	120	T	Effect	26	45%
T	58	M	Effect	26	98%
T	42	M	Effect	-52	89%
T	42	M	Effect	96	75%
T	58	I	Effect	79	96%
R	12	P	Neutral	96	54%
R	12	P	Neutral	56	26%
Y	182	F	Neutral	25	78%
Y	223	F	Effect	36	96%
Y	201	F	Effect	24	54%
Y	207	F	Effect	75	26%
Y	117	F	Neutral	98	98%
K	152	K	Effect	85	98%
K	146	K	Effect	96	78%
K	168	K	Effect	86	98%
K	146	N	Effect	56	76%
K	168	N	Effect	24	98%
K	152	N	Effect	98	78%
L	379	P	Effect	75	98%
L	401	P	Effect	65	76%
L	385	P	Effect	42	98%
L	295	P	Effect	35	78%
L	360	P	Neutral	-29	98%
Y	137	C	Neutral	56	76%
Y	131	C	Neutral	36	98%
Y	153	C	Effect	75	78%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs137853593	Probably damaging	0.999
rs137853593	Probably damaging	0.999
rs137853593	Possibly damaging	1.00
rs137853593	Probably damaging	0.999
rs137853593	Probably damaging	0.98
rs137853594	Possibly damaging	0.98
rs137853594	Possibly damaging	1.00
rs137853594	Probably damaging	0.999
rs137853596	Possibly damaging	1.00
rs137853596	Probably damaging	0.98
rs137853596	Possibly damaging	1.00
rs137853596	Probably damaging	0.999
rs137853596	Possibly damaging	0.98
rs137853597	Probably damaging	1.00
rs137853597	Probably damaging	0.999
rs137853597	Probably damaging	0.999
rs137853597	Probably damaging	0.999
rs137853597	Possibly damaging	1.00
rs141068211	Probably damaging	0.999
rs141068211	Probably damaging	0.98
rs141068211	Possibly damaging	0.98
rs141068211	Possibly damaging	1.00
rs141068211	Probably damaging	0.98
rs145873635	Possibly damaging	1.00
rs145873635	Probably damaging	0.999
rs145873635	Possibly damaging	1.00
rs145873635	Probably damaging	0.98
rs147896487	Probably damaging	0.98
rs147896487	Probably damaging	0.999
rs150268016	Probably damaging	0.999
rs150268016	Possibly damaging	0.999
rs150268016	Possibly damaging	1.00
rs150268016	Probably damaging	0.999
rs150268016	Probably damaging	0.999
rs200455852	Possibly damaging	1.00
rs200455852	Probably damaging	0.98
rs200455852	Probably damaging	0.98
rs200455852	Possibly damaging	1.00
rs200455852	Possibly damaging	0.98
rs200455852	Possibly damaging	1.00
rs368345612	Probably damaging	0.999
rs368345612	Probably damaging	0.98
rs368345612	Possibly damaging	0.98
rs368345612	Possibly damaging	1.00
rs368345612	Probably damaging	0.98
rs371666412	Possibly damaging	1.00

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs137853593	ASAH1_T238K	Uniprot Residue:V	T238K	Medium	2.96
rs137853593	ASAH1_T216K		T216K	High	6.94
rs137853593	ASAH1_T222K		T222K	High	11.6
rs137853593	ASAH1_T197K		T197K	Low	0.32
rs137853593	ASAH1_T132K		T132K	Low	1.5
rs137853594	ASAH1_E138V	Uniprot Residue:A	E138V	High	5.02
rs137853594	ASAH1_E132V		E132V	High	6.73
rs137853594	ASAH1_E154V		E154V	Low	0.98
rs137853596	ASAH1_N320D		N320D	Medium	4.56
rs137853596	ASAH1_N314D	Uniprot Residue:I	N314D	Medium	3.67
rs137853596	ASAH1_N336D		N336D	Medium	2.86
rs137853596	ASAH1_N230D		N230D	Low	0.32
rs137853596	ASAH1_N295D		N295D	Low	1.5
rs137853597	ASAH1_L176V	Uniprot Residue:C	L176V	High	5.02
rs137853597	ASAH1_L198V		L198V	High	6.73
rs137853597	ASAH1_L182V	Uniprot Residue:T	L182V	High	8.52
rs137853597	ASAH1_L92V		L92V	High	6.62
rs137853597	ASAH1_L157V		L157V	Medium	2.16
rs141068211	ASAH1_M185T		M185T	Low	0.82
rs141068211	ASAH1_M204T		M204T	High	7.88
rs141068211	ASAH1_M226T		M226T	Low	0.32
rs141068211	ASAH1_M210T		M210T	Medium	2.96
rs141068211	ASAH1_M120T	Uniprot Residue:A	M120T	High	6.94
rs145873635	ASAH1_T58M		T58M	High	11.6
rs145873635	ASAH1_T42M		T42M	Low	0.32
rs145873635	ASAH1_T42M		T42M	Low	1.5
rs145873635	ASAH1_T58I		T58I	High	5.02
rs147896487	ASAH1_R12P		R12P	High	6.73
rs147896487	ASAH1_R12P		R12P	High	8.52
rs150268016	ASAH1_Y182F		Y182F	High	6.62
rs150268016	ASAH1_Y223F		Y223F	Medium	2.16
rs150268016	ASAH1_Y201F	Uniprot Residue:M	Y201F	Low	0.82
rs150268016	ASAH1_Y207F		Y207F	Low	1.5

10. Active Site

Nil

11. Primary Sequence Analysis

Number of amino acids

395

Molecular weight

44659.64

Theoretical pI

7.52

Amino acid composition

Ala (A) 19 4.8%

Arg (R) 16 4.1%

Asn (N) 22 5.6%

Asp (D) 20 5.1%

Cys (C) 8 2.0%

Gln (Q) 9 2.3%

Glu (E) 21 5.3%

Gly (G) 29 7.3%

His (H) 5 1.3%

Ile (I) 24 6.1%

Leu (L) 41 10.4%

Lys (K) 26 6.6%

Met (M) 10 2.5%

Phe (F) 20 5.1%

Pro (P) 23 5.8%

Ser (S) 19 4.8%

Thr (T) 30 7.6%

Trp (W) 10 2.5%

Tyr (Y) 15 3.8%

Val (V) 28 7.1%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

Total number of negatively charged residues (Asp + Glu)

Total number of positively charged residues (Arg + Lys)

Formula

C₂₀₃₆H₃₁₅₂N₅₂₀O₅₇₃S₁₈

Total number of atoms

6299

Instability index(II)

38.48

Stability

stable

Aliphatic index(AI)

89.54

GRAVY

-0.111

12. Secondary structure analysis

Alpha helix (Hh) : 143 is 36.20%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 70 is 17.72%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 182 is 46.08%

Ambiguous states (?) : 0 is 0.00%

Other states : 0 is 0.00%

Secondary Structure Prediction

Amino Acid Type

13. Enzymes

Name of enzyme	No. of cleavages
Arg-C proteinase	16
Asp-N endopeptidase	20
Asp-N endopeptidase + N-terminal Glu	41
BNPS-Skatole	10
CNBr	10
Chymotrypsin-high specificity (C-term to [FYW], not before P)	43
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	94
Clostripain	16
Formic acid	20
Glutamyl endopeptidase	21
Iodosobenzoic acid	10
Hydroxylamine	1
LysC	26
LysN	26
NTCB (2-nitro-5-thiocyanobenzoic acid)	8
Pepsin (pH1.3)	87
Pepsin (pH>2)	117
Proline-endopeptidase	4
Proteinase K	208
Staphylococcal peptidase I	18
Thermolysin	119
Trypsin	38

14. Epitope

Rank	Start position	Sequence	Score	Prediction
1	245	DVMWIGFLTRTVLENS	0.92	Epitope
2	41	PTYRGAVPWYTINLDL	0.91	Epitope
3	279	AYFILGGNQSGEGCVI	0.90	Epitope
4	81	KNMINTFVPSGKIMQV	0.88	Epitope
4	321	YDRWKHPFFLDDRRTP	0.88	Epitope
4	205	AGYVGMLTGFKPGLFS	0.88	Epitope
4	152	KGHLIHGRNMDFGVFL	0.88	Epitope
5	175	TWVITEQLKPLTVNLD	0.87	Epitope
6	263	YEEAKNLLTKTKILAP	0.86	Epitope
7	291	GCVITRDRKESLDVYE	0.84	Epitope
8	356	DVLSTKPVLNKLTVYT	0.83	Epitope
8	327	PFFLDDRRTPAKMCLN	0.83	Epitope
9	377	TKGQFETYLRDCPDPC	0.82	Epitope
9	272	KTKILAPAYFILGGNQ	0.82	Epitope
10	350	SFETMYDVLSTKPVLN	0.81	Epitope
10	298	RKESLDVYELDAKQGR	0.81	Epitope
10	253	TRTVLENSTSYEEAKN	0.81	Epitope
11	94	MQVVDEKLPGLLGNFP	0.80	Epitope
12	23	HAPPWTEDCRKSTYPP	0.79	Epitope
13	127	LGEIISFNIFYELFTI	0.78	Epitope
14	59	YKRWHELMLDKAPVLK	0.77	Epitope
14	115	EMKGIAAVTDIPLGEI	0.77	Epitope
15	49	WYTINLDLPPYKRWHE	0.74	Epitope
16	146	IVAEDKKGHLIHGRNM	0.73	Epitope
17	109	PGPFEEEMKGIAAVTD	0.72	Epitope
18	309	AKQGRWYVVQTNYDRW	0.70	Epitope
18	226	RFSINGGYLGILEWIL	0.70	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	51
Avg node degree	9.27
avg. local clustering coefficient	0.943
expected number of edges	10
p-value	< 1.0e-16
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot