ClinVar

Description

Variant summary: CYP17A1 c.3G>A (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. An alternative downstream in-frame start codon (Met 49) is located in the encoded protein. An activation of potential downstream translation initiation site would result in a shortened protein missing the first 48 amino acids from the protein sequence. Other pathogenic variants has been reported upstream of this alternate codon in the HGMD database. Additionally, two other initiation codon variants, namely c.3G>C and c.2T>C have also been reported in association with Steroid-17 alpha hydroxylase deficiency in the HGMD database. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250590 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3G>A has been reported in the literature in one allele of at-least one individual affected with Congenital Adrenal Hyperplasia (example, Wang_2021). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.