ClinVar

Description

A Homozygote Missense variant c.1247G>A in Exon 8 of the CYP17A1 gene that results in the amino acid substitution p.Arg416His was identified. The observed variant has a minor allele frequency of 0.00003% in gnomAD genomes. The severity of the impact of this variant on the protein is medium, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Likely Pathogenic (Variant ID-1804). This variant has been previously reported in Ergun-Longmire B et al., 2006. Expression studies revealed no detectable activity of the encoded protein (Ergun-Longmire B et al., 2006). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.