Variant 12-52057379-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173157.3(NR4A1):c.1389C>G(p.Ile463Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NR4A1
NM_173157.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781

Variant links:

Genes affected

NR4A1 (HGNC:7980): (nuclear receptor subfamily 4 group A member 1) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

NR4A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A1	NM_173157.3 linkuse as main transcript	c.1389C>G	p.Ile463Met	missense_variant	6/7	ENST00000394825.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A1	ENST00000394825.6 linkuse as main transcript	c.1389C>G	p.Ile463Met	missense_variant	6/7	1	NM_173157.3	P1	P22736-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251304

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1428C>G (p.I476M) alteration is located in exon 7 (coding exon 6) of the NR4A1 gene. This alteration results from a C to G substitution at nucleotide position 1428, causing the isoleucine (I) at amino acid position 476 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.029

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.94

D;D;.;.;D;.

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.59

D;D;D;D;D;D

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0040

D;T;D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D

Polyphen

0.18

.;.;.;B;B;B

Vest4

0.67

MutPred

0.57

.;.;.;Gain of disorder (P = 0.0536);Gain of disorder (P = 0.0536);Gain of disorder (P = 0.0536);

MVP

0.44

MPC

0.77

ClinPred

0.84

GERP RS

3.3

Varity_R

0.72

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over