ClinVar Miner

Submissions for variant NM_004959.5(NR5A1):c.571C>T (p.Arg191Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV004556119 SCV005045228 uncertain significance 46,XY sex reversal 3 2024-05-16 criteria provided, single submitter curation The heterozygous p.Arg191Cys variant in NR5A1 was identified by our study in one individual with 46XY sex reversal 3. The p.Arg191Cys variant has been reported in one individual with spermatogenic failure (PMID: 20887963), and has been identified in 0.002% (1/51762) of Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP (rs1253324106)). In vitro functional studies provide some evidence that the p.Arg191Cys variant may slightly impact protein function (PMID: 20887963). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg191Cys variant is uncertain. ACMG/AMP Criteria applied: PS4_Supporting, PM2_Supporting, PS3_Supporting, PP3_Moderate (Richards 2015).

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