12-52054815-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173157.3(NR4A1):c.487C>T(p.Pro163Ser) 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 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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
NM_173157.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 2.00
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20057079).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NR4A1 | NM_173157.3 | c.487C>T | p.Pro163Ser | 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.487C>T | p.Pro163Ser | missense_variant | 2/7 | 1 | NM_173157.3 | ENSP00000378302 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461230Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726926
GnomAD4 exome
AF:
AC:
1
AN:
1461230
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726926
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
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 | Oct 26, 2022 | The c.526C>T (p.P176S) 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 526, causing the proline (P) at amino acid position 176 to be replaced by a serine (S). 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
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;T;T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;.;.;T;.;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;N;N;N;N;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;D;N;N;N;N;N;N;D
REVEL
Uncertain
Sift
Benign
D;D;D;D;T;T;T;D;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
0.71
.;.;.;.;P;P;P;.;.
Vest4
MutPred
0.27
.;.;.;.;Loss of glycosylation at S162 (P = 0.1006);Loss of glycosylation at S162 (P = 0.1006);Loss of glycosylation at S162 (P = 0.1006);Loss of glycosylation at S162 (P = 0.1006);.;
MVP
MPC
ClinPred
T
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