ClinVar Miner

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

gnomAD frequency: 0.00003  dbSNP: rs763296857
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534325 SCV000631424 pathogenic 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency 2023-09-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SRD5A2 function (PMID: 8110760). 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. ClinVar contains an entry for this variant (Variation ID: 459638). 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. This variant is present in population databases (rs763296857, gnomAD 0.003%). 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).
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)

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