Variant X-30834092-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152787.5(TAB3):c.1949T>G(p.Val650Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,209,912 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 62 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V650E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 62 hem. )

Consequence

TAB3
NM_152787.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

TAB3 (HGNC:30681): (TGF-beta activated kinase 1 (MAP3K7) binding protein 3) The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TAB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018006682).

BS2

High Hemizygotes in GnomAdExome4 at 62 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB3	NM_152787.5 linkuse as main transcript	c.1949T>G	p.Val650Gly	missense_variant	10/11	ENST00000288422.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB3	ENST00000288422.4 linkuse as main transcript	c.1949T>G	p.Val650Gly	missense_variant	10/11	5	NM_152787.5	P1	Q8N5C8-1
TAB3	ENST00000378930.7 linkuse as main transcript	c.1949T>G	p.Val650Gly	missense_variant	6/7	1		P1	Q8N5C8-1
TAB3	ENST00000378933.5 linkuse as main transcript	c.1949T>G	p.Val650Gly	missense_variant	11/12	1		P1	Q8N5C8-1
TAB3	ENST00000378932.6 linkuse as main transcript	c.1865T>G	p.Val622Gly	missense_variant	10/11	1			Q8N5C8-2

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111769

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33929

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

183234

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

67682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000894

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

122

AN:

1098088

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

363446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000570

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000626

AC:

AN:

111824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33994

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

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

Dec 28, 2023

The c.1949T>G (p.V650G) alteration is located in exon 10 (coding exon 6) of the TAB3 gene. This alteration results from a T to G substitution at nucleotide position 1949, causing the valine (V) at amino acid position 650 to be replaced by a glycine (G). 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

0.096

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;.

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.51

.;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.48

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0090

D;D;D

Sift4G

Benign

0.48

T;T;T

Polyphen

0.099

B;B;B

Vest4

0.11

MVP

0.51

MPC

0.52

ClinPred

0.056

GERP RS

3.5

Varity_R

0.12

gMVP

0.47

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.

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