9-124503172-C-T

Variant names:

• chr9-124503172-C-T
• rs775441984
• NM_004959.5:c.151G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004959.5(NR5A1):​c.151G>A​(p.Glu51Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR5A1 NM_004959.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A1	NM_004959.5	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A1	ENST00000373588.9	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 7	1	NM_004959.5	ENSP00000362690.4
NR5A1	ENST00000620110.4	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 6	5		ENSP00000483309.1
NR5A1	ENST00000455734.1	c.151G>A	p.Glu51Lys	missense_variant	Exon 3 of 4	3		ENSP00000393245.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448230 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719386

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.89	.;D;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Benign	-0.030	.;N;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0090	.;D;T
Sift4G	Benign	0.081	T;T;.
Polyphen		0.70	.;P;.
Vest4		0.55
MutPred		0.48		Gain of methylation at E51 (P = 0.0071);Gain of methylation at E51 (P = 0.0071);Gain of methylation at E51 (P = 0.0071);
MVP		0.81
MPC		1.7
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.75
gMVP		0.90

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

LitVar

Other links and lift over

dbSNP: rs775441984; hg19: chr9-127265451;