rs762916063

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025228.4(TRAF3IP3):​c.8G>A​(p.Ser3Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TRAF3IP3
NM_025228.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.938
Variant links:
Genes affected
TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06191933).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRAF3IP3NM_025228.4 linkc.8G>A p.Ser3Asn missense_variant Exon 3 of 17 ENST00000367025.8 NP_079504.2 Q9Y228-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRAF3IP3ENST00000367025.8 linkc.8G>A p.Ser3Asn missense_variant Exon 3 of 17 1 NM_025228.4 ENSP00000355992.3 Q9Y228-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.046
T;T;T;.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.52
T;.;T;T;T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.062
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M;.;M;M
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.56
N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.27
T;T;.;T;T
Sift4G
Benign
0.46
T;T;T;T;T
Polyphen
0.14
B;B;.;B;B
Vest4
0.084
MutPred
0.063
Loss of phosphorylation at S3 (P = 0.0073);Loss of phosphorylation at S3 (P = 0.0073);Loss of phosphorylation at S3 (P = 0.0073);Loss of phosphorylation at S3 (P = 0.0073);Loss of phosphorylation at S3 (P = 0.0073);
MVP
0.37
MPC
0.12
ClinPred
0.076
T
GERP RS
2.4
Varity_R
0.022
gMVP
0.27

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

LitVar

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

Other links and lift over

dbSNP: rs762916063; hg19: chr1-209933392; COSMIC: COSV99162745; API