Submissions for variant NM_004959.5(NR5A1):c.1106_1109del (p.Val369fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003008127	SCV003312647	pathogenic	Oligosynaptic infertility; 46,XY disorder of sex development	2022-02-02	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NR5A1 protein in which other variant(s) (p.Tyr409*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with NR5A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val369Alafs*12) in the NR5A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the NR5A1 protein.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003128165	SCV003804321	pathogenic	46,XY sex reversal 3	2023-02-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003404007	SCV004103733	likely pathogenic	NR5A1-related disorder	2023-09-05	criteria provided, single submitter	clinical testing	The NR5A1 c.1106_1109delTCTG variant is predicted to result in a frameshift and premature protein termination (p.Val369Alafs*12). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in NR5A1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.