rs669694

chr1-209777415-C-Achr1-209777415-C-Gchr1-209777415-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025228.4(TRAF3IP3):c.1117C>A(p.Gln373Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. Q373E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95

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 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=0.1193313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4	c.1117C>A	p.Gln373Lys	missense_variant	12/17	ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.1117C>A	p.Gln373Lys	missense_variant	12/17	1	NM_025228.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.010	T;T;.;T;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.29	T;.;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.71	N;N;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;D;D;D
Polyphen		0.0010	B;B;B;B;.;.
Vest4		0.12
MutPred		0.13		.;Gain of ubiquitination at Q373 (P = 0.0109);.;Gain of ubiquitination at Q373 (P = 0.0109);.;.;
MVP		0.66
MPC		0.16
ClinPred		0.75	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.086

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: rs669694; hg19: chr1-209950760;