Variant 9-124482921-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_004959.5(NR5A1):c.1223A>C(p.His408Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 30)

Consequence

NR5A1
NM_004959.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.33

Variant links:

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]

NR5A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 9-124482921-T-G is Pathogenic according to our data. Variant chr9-124482921-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1202604.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR5A1	NM_004959.5 linkuse as main transcript	c.1223A>C	p.His408Pro	missense_variant	7/7	ENST00000373588.9	NP_004950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NR5A1	ENST00000373588.9 linkuse as main transcript	c.1223A>C	p.His408Pro	missense_variant	7/7	1	NM_004959.5	ENSP00000362690	P1
NR5A1	ENST00000620110.4 linkuse as main transcript	c.1103A>C	p.His368Pro	missense_variant	6/6	5		ENSP00000483309
NR5A1	ENST00000373587.3 linkuse as main transcript	c.575A>C	p.His192Pro	missense_variant	5/5	3		ENSP00000362689

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Disorder of sexual differentiation

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Human Developmental Genetics, Institut Pasteur

Aug 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.86

.;D;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.79

T;T;T

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Pathogenic

0.87

MutationAssessor

Uncertain

2.2

.;M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

.;N;D

REVEL

Pathogenic

0.77

Sift

Benign

0.18

.;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.96

.;P;.

Vest4

0.50

MutPred

0.50

.;Loss of helix (P = 0.1299);.;

MVP

0.84

MPC

1.2

ClinPred

0.92

GERP RS

5.1

Varity_R

0.96

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over