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Table 3 Evaluation of pathogenicity of novel variants using in-silico prediction tools

From: Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Gene Mutation Protein change Mutation taster LRT SIFT PROVEAN DANN ExAC dbSNP
ASS1 c.190G > A p.Val64Ile Disease causing Neutral Tolerated Neutral 0.9791 0.00003303 556,297,791
c.269G > A p.Gly90Asp Disease causing Unknown Damaging Damaging 0.9985 Not Present 1,422,867,920
c.271A > C p.Thr91Pro Disease causing Unknown Damaging Damaging 0.9963 0.00003324 769,018,733
c.570C > A p.Tyr190Ter Disease causing Unknown NA NA 0.9957 Not Present Not Present
c.1139delA p.Gln380Argfs*20 Disease causing NA NA NA NA Not Present 1,213,378,896
ASL c.89_94delinsGTCGTA p.Tyr30_Asp31delinsCysArg Disease causing NA NA NA NA Not present Not present
c.326C > G p.Thr109Arg Disease causing Deleterious Damaging Damaging 0.9938 Not present Not Present
c.593C > T p.Pro198Leu Disease causing Deleterious Damaging Damaging 0.9992 Not Present 1,282,829,485
c.649C > T p.Arg217Ter Disease causing Neutral NA NA 0.9972 0.000008443 369,879,957
c.733T > C p.Trp245Arg Disease causing Deleterious Damaging Damaging 0.9941 Not present Not Present
c.749T > A p.Met250Lys Disease causing Deleterious Damaging Damaging 0.9791 Not present 754,634,171
c.913G > A p.Gly305Arg Disease causing Deleterious Damaging Damaging 0.9993 Not present Not Present
c.967A > G p.Lys323Glu Disease causing Deleterious Damaging Damaging 0.9987 Not present Not Present
OTC c.773_790del p.Asn258_263Del Disease causing NA NA NA NA Not present Not Present
c.805G > A p.Gly269Arg Disease causing Deleterious Damaging Damaging 0.9992 Not Present Not Present
ARG1 c.2T > C p.Met1Thr Disease causing Deleterious Damaging Neutral 0.9809 Not Present Not Present
c.132_146del p.Gln44_Lys48del Disease causing NA NA NA NA Not Present Not Present
c.295G > A p.Gly99Arg Disease causing Deleterious Damaging Damaging 0.9993 0.00001658 753,829,097
c.551delC p.Pro184Leufs*7 Disease causing NA NA NA NA Not Present Not Present
c.802 + 2 T > G Splice site Disease causing NA NA NA 0.9948 Not Present Not Present
c.877delG p.Val293Ter Disease causing NA NA NA NA Not Present Not Present
CPS1 c.254 + 4A > G Splice site Disease causing NA NA NA 0.9747 Not Present Not Present
NAGS c.787G > T p.Glu263Ter Disease causing Deleterious NA NA 0.9963 Not Present Not Present
c.991C > T p.Gln331Ter Disease causing Deleterious NA NA 0.9973 Not Present 1,445,639,047
  1. Mutation Taster: An in silico prediction tool for the pathogenicity of a variant based on evolutionary conservation, splice-site, mRNA, protein and regulatory features. The potential is predicted by a naive Bayes classifier
  2. LRT: Likelihood ratio test (LRT) predicts deleterious variants through identification of highly conserved amino acid regions using a comparative genomics data set of 32 vertebrate species. Range 0 to 1
  3. SIFT: SIFT (sorts intolerant from tolerant) is an in silico prediction tool for nonsynonymous variants based on sequence homology derived from closely related sequences collected through PSI-BLAST. Range 0 to 1 with values less than 0.05 usually considered intolerant. 40% of the values in this database are below 0.01
  4. PROVEAN: Protein Variation Effect Analyzer is an in silico tool that predicts how nonsynonymous, MNP, or in-frame indel variant will affect a protein’s biological function. The prediction is based on alignment-based scores derived from pairwise sequence alignments between the query sequence and each of the related sequences at the protein level. Range − 14 to + 14
  5. DANN: DANN is a pathogenicity scoring methodology developed by Daniel Quang, Yifei Chen and Xiaohui Xie at the University of California, Irvine. It is based on deep neural networks. The value range is 0 to 1, with 1 given to the variants predicted to be the most damaging
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172