Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002223055 | SCV002500674 | likely pathogenic | Congenital adrenal hyperplasia | 2022-03-28 | criteria provided, single submitter | clinical testing | 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. |
| Fulgent Genetics, |
RCV002502035 | SCV002811504 | likely pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2022-05-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003774647 | SCV004663228 | likely pathogenic | not provided | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the CYP17A1 mRNA. The next in-frame methionine is located at codon 49. This variant is present in population databases (rs61754262, gnomAD 0.003%). Disruption of the initiator codon has been observed in individual(s) with 17-alpha-hydroxylase deficiency and/or clinical features of CYP17A1-related conditions (PMID: 9855540, 14715827, 33864926, 35729303). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1677197). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |