Variant X-30854949-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152787.5(TAB3):c.716C>T(p.Ser239Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00135 in 1,206,542 control chromosomes in the GnomAD database, including 3 homozygotes. There are 539 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 61 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 3 hom. 478 hem. )

Consequence

TAB3
NM_152787.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.78

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006741613).

BP6

Variant X-30854949-G-A is Benign according to our data. Variant chrX-30854949-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790384.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 61 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB3	NM_152787.5 linkuse as main transcript	c.716C>T	p.Ser239Leu	missense_variant	6/11	ENST00000288422.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB3	ENST00000288422.4 linkuse as main transcript	c.716C>T	p.Ser239Leu	missense_variant	6/11	5	NM_152787.5	P1	Q8N5C8-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

157

AN:

111529

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

AN XY:

33681

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000953

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00144

AC:

250

AN:

173748

Hom.:

AF XY:

0.00140

AC XY:

AN XY:

59376

show subpopulations

Gnomad AFR exome

AF:

0.000160

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00882

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000921

GnomAD4 exome

AF:

0.00134

AC:

1469

AN:

1095013

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

478

AN XY:

360633

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.00902

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00141

AC:

157

AN:

111529

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

AN XY:

33681

show subpopulations

Gnomad4 AFR

AF:

0.000196

Gnomad4 AMR

AF:

0.0000953

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.00145

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000699

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000892

AC:

ExAC

AF:

0.00143

AC:

173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.084

B;B;B

Vest4

0.23

MVP

0.57

MPC

0.38

ClinPred

0.041

GERP RS

4.9

Varity_R

0.41

gMVP

0.49

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