ClinVar Miner

Submissions for variant NM_004959.5(NR5A1):c.274C>T (p.Arg92Trp)

dbSNP: rs886039769
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital RCV000256210 SCV000322734 likely pathogenic 46,XY sex reversal 3 2016-09-30 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network, NIH RCV000490553 SCV000622150 uncertain significance 46,XX sex reversal 4 2016-03-23 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our study inferred de novo in a 31-year-old 46,XX male with hypogonadism, decreased testicular size, and primary testicular failure. This patient has been reported in PMID 27378692.
Genetic Services Laboratory, University of Chicago RCV001820799 SCV002072100 pathogenic not provided 2017-08-04 criteria provided, single submitter clinical testing
Invitae RCV001855015 SCV002243305 pathogenic Oligosynaptic infertility; 46,XY disorder of sex development 2021-09-16 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 265792). This missense change has been observed in individual(s) with NR5A1-related conditions (PMID: 27378692, 27490115, 28033660). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 92 of the NR5A1 protein (p.Arg92Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NR5A1 function (PMID: 27378692).
OMIM RCV000490553 SCV000579208 pathogenic 46,XX sex reversal 4 2021-04-23 no assertion criteria provided literature only
OMIM RCV000256210 SCV000579209 pathogenic 46,XY sex reversal 3 2021-04-23 no assertion criteria provided literature only

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