Variant chrX-30854485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152787.5(TAB3):c.1180C>T(p.Arg394Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,209,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000068 ( 0 hom. 23 hem. )

Consequence

TAB3
NM_152787.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73

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:

TAB3-AS2 (HGNC:40013): (TAB3 antisense RNA 2)

TAB3-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28277123).

BS2

High Hemizygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB3	NM_152787.5 linkuse as main transcript	c.1180C>T	p.Arg394Trp	missense_variant	6/11	ENST00000288422.4	NP_690000.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAB3	ENST00000288422.4 linkuse as main transcript	c.1180C>T	p.Arg394Trp	missense_variant	6/11	5	NM_152787.5	ENSP00000288422	P1	Q8N5C8-1
TAB3-AS2	ENST00000445240.1 linkuse as main transcript	n.70G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33728

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000754

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000683

AC:

AN:

1097819

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

363199

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000832

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000359

AC:

AN:

111544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33728

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000754

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000359

Hom.:

Bravo

AF:

0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

LIST_S2

Uncertain

0.96

.;D;D

MetaRNN

Benign

0.28

T;T;T

Sift4G

Uncertain

0.018

D;D;D

Vest4

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.64

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over