Variant 12-52054876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173157.3(NR4A1):c.548C>T(p.Pro183Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NR4A1
NM_173157.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.446

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107733905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A1	NM_173157.3 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	2/7	ENST00000394825.6	NP_775180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000394825.6 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	2/7	1	NM_173157.3	ENSP00000378302	P1	P22736-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727174

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 09, 2021

The c.587C>T (p.P196L) alteration is located in exon 3 (coding exon 2) of the NR4A1 gene. This alteration results from a C to T substitution at nucleotide position 587, causing the proline (P) at amino acid position 196 to be replaced by a leucine (L). 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

Benign

0.068

BayesDel_addAF

Benign

0.0035

BayesDel_noAF

Benign

-0.23

CADD

Benign

5.8

DANN

Benign

0.79

DEOGEN2

Benign

0.33

.;T;.;.;T;T;T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.74

T;T;T;.;.;T;.;T;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.69

.;.;.;.;N;N;N;N;.

MutationTaster

Benign

0.96

D;D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N;D

REVEL

Benign

0.23

Sift

Benign

0.047

D;T;D;D;T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T;T;T;T;D

Polyphen

0.0

.;.;.;.;B;B;B;.;.

Vest4

0.088

MutPred

0.25

.;.;.;.;Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);.;

MVP

0.65

MPC

0.37

ClinPred

0.027

GERP RS

0.66

Varity_R

0.041

gMVP

0.40

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