12-52054449-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173157.3(NR4A1):āc.121G>Cā(p.Glu41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
NR4A1
NM_173157.3 missense
NM_173157.3 missense
Scores
12
7
Clinical Significance
Conservation
PhyloP100: 6.66
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]
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ACMG classification
Classification made for transcript
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NR4A1 | NM_173157.3 | c.121G>C | p.Glu41Gln | 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 | c.121G>C | p.Glu41Gln | missense_variant | 2/7 | 1 | NM_173157.3 | ENSP00000378302 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250974Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135678
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727026
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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 26, 2023 | The c.160G>C (p.E54Q) alteration is located in exon 3 (coding exon 2) of the NR4A1 gene. This alteration results from a G to C substitution at nucleotide position 160, causing the glutamic acid (E) at amino acid position 54 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;T;T;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;.;.;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;.;.;.;.;L;L;.;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;T;T;T;T;T;D;T;T;T
Sift4G
Uncertain
D;T;T;T;T;T;T;D;T;T;T
Polyphen
0.29
.;.;.;.;.;B;B;.;B;.;.
Vest4
0.17, 0.13, 0.18, 0.15, 0.13, 0.12, 0.41
MutPred
0.13
.;.;.;.;.;Loss of phosphorylation at S39 (P = 0.096);Loss of phosphorylation at S39 (P = 0.096);Loss of phosphorylation at S39 (P = 0.096);Loss of phosphorylation at S39 (P = 0.096);Loss of phosphorylation at S39 (P = 0.096);.;
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at