ClinVar Miner

Submissions for variant NM_000348.4(SRD5A2):c.578A>G (p.Asn193Ser)

gnomAD frequency: 0.00003  dbSNP: rs763296857
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534325 SCV000631424 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2024-05-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 193 of the SRD5A2 protein (p.Asn193Ser). This variant is present in population databases (rs763296857, gnomAD 0.003%). This missense change has been observed in individual(s) with ambiguous genitalia and 5 alpha-reductase deficiency (PMID: 20019388, 20736251, 20850730, 21631525, 23633205, 24665940). 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: 459638). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SRD5A2 protein function. Experimental studies have shown that this missense change affects SRD5A2 function (PMID: 8110760). For these reasons, this variant has been classified as Pathogenic.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000534325 SCV000692392 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2017-10-31 criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269600 SCV001449696 likely pathogenic not provided 2017-08-18 criteria provided, single submitter clinical testing
GeneDx RCV001269600 SCV002578683 pathogenic not provided 2022-04-04 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on enzymatic function (Wigley et al., 1994); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 3441728, 8110760, 31613402, 32894851, 27899157, 7608269, 30695888, 31031332, 32596280, 20850730, 28544750, 34276780)
Fulgent Genetics, Fulgent Genetics RCV000534325 SCV005663648 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2024-05-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.