1-209777415-C-G

Variant names:

• chr1-209777415-C-G
• rs669694
• NM_025228.4:c.1117C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025228.4(TRAF3IP3):​c.1117C>G​(p.Gln373Glu) variant causes a missense change. The variant allele was found at a frequency of 0.795 in 1,613,380 control chromosomes in the GnomAD database, including 510,605 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50513 hom., cov: 31)
  • Exomes 𝑓: 0.79 (460092 hom.)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5512646E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4	c.1117C>G	p.Gln373Glu	missense_variant	Exon 12 of 17	ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.1117C>G	p.Gln373Glu	missense_variant	Exon 12 of 17	1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123661 AN: 151936 Hom.: 50478 Cov.: 31

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.812

GnomAD2 exomes AF: 0.791 AC: 198762 AN: 251162 AF XY: 0.789

Gnomad AFR exome AF: 0.868

Gnomad AMR exome AF: 0.791

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.804

Gnomad FIN exome AF: 0.745

Gnomad NFE exome AF: 0.787

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.793 AC: 1159180 AN: 1461326 Hom.: 460092 Cov.: 48 AF XY: 0.793 AC XY: 576194 AN XY: 726938

African (AFR) AF: 0.869 AC: 29076 AN: 33474

American (AMR) AF: 0.792 AC: 35406 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 21318 AN: 26116

East Asian (EAS) AF: 0.822 AC: 32596 AN: 39666

South Asian (SAS) AF: 0.786 AC: 67689 AN: 86170

European-Finnish (FIN) AF: 0.747 AC: 39855 AN: 53384

Middle Eastern (MID) AF: 0.830 AC: 4770 AN: 5750

European-Non Finnish (NFE) AF: 0.792 AC: 880573 AN: 1111702

Other (OTH) AF: 0.793 AC: 47897 AN: 60372

GnomAD4 genome AF: 0.814 AC: 123753 AN: 152054 Hom.: 50513 Cov.: 31 AF XY: 0.811 AC XY: 60250 AN XY: 74300

African (AFR) AF: 0.867 AC: 35982 AN: 41494

American (AMR) AF: 0.824 AC: 12597 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2835 AN: 3468

East Asian (EAS) AF: 0.809 AC: 4153 AN: 5136

South Asian (SAS) AF: 0.787 AC: 3781 AN: 4804

European-Finnish (FIN) AF: 0.746 AC: 7878 AN: 10558

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53870 AN: 67982

Other (OTH) AF: 0.808 AC: 1709 AN: 2114

Alfa AF: 0.793 Hom.: 36106

Bravo AF: 0.819

TwinsUK AF: 0.788 AC: 2922

ALSPAC AF: 0.789 AC: 3040

ESP6500AA AF: 0.857 AC: 3778

ESP6500EA AF: 0.799 AC: 6870

ExAC AF: 0.790 AC: 95898

Asia WGS AF: 0.763 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.0040	T;T;.;T;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.032	T;.;T;T;T;T
MetaRNN	Benign	5.6e-7	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.3	.;N;.;N;.;.
PhyloP100		3.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.9	N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;.;.
Vest4		0.047
MPC		0.13
ClinPred		0.013	T
GERP RS		5.6
Varity_R		0.11
gMVP		0.024
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs669694; hg19: chr1-209950760; COSMIC: COSV50560315; COSMIC: COSV50560315;