Variant chr1-209762660-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025228.4(TRAF3IP3):c.491G>T(p.Arg164Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 1,344,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

TRAF3IP3
NM_025228.4 missense, splice_region

Scores

Splicing: ADA: 0.00003611

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.315

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]

TRAF3IP3 links:

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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=0.060400426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4 linkuse as main transcript	c.491G>T	p.Arg164Leu	missense_variant, splice_region_variant	4/17	ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8 linkuse as main transcript	c.491G>T	p.Arg164Leu	missense_variant, splice_region_variant	4/17	1	NM_025228.4	P1	Q9Y228-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

75896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000324

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000473

AC:

AN:

1268990

Hom.:

Cov.:

AF XY:

0.00000483

AC XY:

AN XY:

621586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000404

GnomAD4 genome

AF:

0.0000395

AC:

AN:

75896

Hom.:

Cov.:

AF XY:

0.0000265

AC XY:

AN XY:

37726

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000324

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.00000827

AC:

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

Jun 22, 2024

The c.491G>T (p.R164L) alteration is located in exon 4 (coding exon 2) of the TRAF3IP3 gene. This alteration results from a G to T substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.84

T;.;T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.060

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.3

.;M;.;M

MutationTaster

Benign

0.66

D;D;D;D;D

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.037

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

0.29

B;P;B;P

Vest4

0.28

MutPred

0.29

.;Gain of ubiquitination at K161 (P = 0.0317);.;Gain of ubiquitination at K161 (P = 0.0317);

MVP

0.24

MPC

0.29

ClinPred

0.49

GERP RS

-0.78

Varity_R

0.12

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.064

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over