rs762916063

Variant names:

• chr1-209760047-G-A
• rs762916063
• NM_025228.4:c.8G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-209760047-G-A
• chr1-209760047-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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]

ACMG classification

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
TRAF3IP3	NM_025228.4	c.8G>A	p.Ser3Asn	missense_variant	Exon 3 of 17	ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.8G>A	p.Ser3Asn	missense_variant	Exon 3 of 17	1	NM_025228.4	ENSP00000355992.3

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

Other links and lift over

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