NM_004959.5(NR5A1):c.938G>A (p.Arg313His) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 27, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002527576.4

Allele description [Variation Report for NM_004959.5(NR5A1):c.938G>A (p.Arg313His)]

NM_004959.5(NR5A1):c.938G>A (p.Arg313His)

Gene:

NR5A1:nuclear receptor subfamily 5 group A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q33.3

Genomic location:

Preferred name:

NM_004959.5(NR5A1):c.938G>A (p.Arg313His)

HGVS:

NC_000009.12:g.124493082C>T
NG_008176.1:g.19339G>A
NM_004959.5:c.938G>AMANE SELECT
NP_004950.2:p.Arg313His
NC_000009.11:g.127255361C>T
NM_004959.4:c.938G>A

Protein change:

R313H

Links:

dbSNP: rs1554721235

NCBI 1000 Genomes Browser:

rs1554721235

Molecular consequence:

NM_004959.5:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Oligosynaptic infertility (SPGF1)
Synonyms:: SPERMATOGENIC FAILURE 1; OLIGOCHIASMATIC INFERTILITY
Identifiers:: MONDO: MONDO:0009776; MedGen: C0403810; OMIM: 258150

Name:: 46,XY disorder of sex development
Synonyms:: 46, XY disorder of sex development (DSD)
Identifiers:: MONDO: MONDO:0020040; MedGen: C2751824

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441482	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 27, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22907560, 22028768, 25122490, 27169744, 30425642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441482

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 27, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Preserved fertility in a patient with a 46,XY disorder of sex development due to a new heterozygous mutation in the NR5A1/SF-1 gene: evidence of 46,XY and 46,XX gonadal dysgenesis phenotype variability in multiple members of an affected kindred.

Ciaccio M, Costanzo M, Guercio G, De Dona V, Marino R, Ramirez PC, Galeano J, Warman DM, Berensztein E, Saraco N, Baquedano MS, Chaler E, Maceiras M, Lazzatti JM, Rivarola MA, Belgorosky A.

Horm Res Paediatr. 2012;78(2):119-26. Epub 2012 Aug 14.

PubMed [citation]

PMID:: 22907560

Mutation analysis of NR5A1 encoding steroidogenic factor 1 in 77 patients with 46, XY disorders of sex development (DSD) including hypospadias.

Allali S, Muller JB, Brauner R, Lourenço D, Boudjenah R, Karageorgou V, Trivin C, Lottmann H, Lortat-Jacob S, Nihoul-Fékété C, De Dreuzy O, McElreavey K, Bashamboo A.

PLoS One. 2011;6(10):e24117. doi: 10.1371/journal.pone.0024117. Epub 2011 Oct 20.

PubMed [citation]

PMID:: 22028768
PMCID:: PMC3197579

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441482.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 313 of the NR5A1 protein (p.Arg313His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with NR5A1-related conditions (PMID: 22907560, 30425642). 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. ClinVar contains an entry for this variant (Variation ID: 449434). 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. This variant disrupts the p.Arg313 amino acid residue in NR5A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22028768, 25122490, 27169744, 30425642). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 13, 2025

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