9-124482782-T-C

Position:

• chr9-124482782-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004959.5(NR5A1):​c.1362A>G​(p.Glu454=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: NR5A1 NM_004959.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.64

Genes affected

NR5A1 (HGNC:7983): (nuclear receptor subfamily 5 group A member 1) The protein encoded by this gene is a transcriptional activator involved in sex determination. The encoded protein binds DNA as a monomer. Defects in this gene are a cause of XY sex reversal with or without adrenal failure as well as adrenocortical insufficiency without ovarian defect. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-124482782-T-C is Benign according to our data. Variant chr9-124482782-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1557269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.64 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A1	NM_004959.5	c.1362A>G	p.Glu454=	synonymous_variant	7/7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR5A1	ENST00000373588.9	c.1362A>G	p.Glu454=	synonymous_variant	7/7	1	NM_004959.5	ENSP00000362690	P1
NR5A1	ENST00000620110.4	c.1242A>G	p.Glu414=	synonymous_variant	6/6	5		ENSP00000483309
NR5A1	ENST00000373587.3	c.714A>G	p.Glu238=	synonymous_variant	5/5	3		ENSP00000362689

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 29

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oligosynaptic infertility;C2751824:46,XY disorder of sex development Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127245061;