X-30831560-G-A

Position:

chrX-30831560-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152787.5(TAB3):c.2006C>T(p.Ser669Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,209,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 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 (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000042 ( 0 hom. 13 hem. )

Consequence

TAB3
NM_152787.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11206558).

BS2

High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAB3	NM_152787.5 linkuse as main transcript	c.2006C>T	p.Ser669Phe	missense_variant	11/11	ENST00000288422.4
TAB3	NM_001399872.1 linkuse as main transcript	c.1922C>T	p.Ser641Phe	missense_variant	10/10
TAB3	NM_001399873.1 linkuse as main transcript	c.1904C>T	p.Ser635Phe	missense_variant	10/10
TAB3	XM_047441986.1 linkuse as main transcript	c.2006C>T	p.Ser669Phe	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB3	ENST00000288422.4 linkuse as main transcript	c.2006C>T	p.Ser669Phe	missense_variant	11/11	5	NM_152787.5	P1	Q8N5C8-1
TAB3	ENST00000378930.7 linkuse as main transcript	c.2006C>T	p.Ser669Phe	missense_variant	7/7	1		P1	Q8N5C8-1
TAB3	ENST00000378933.5 linkuse as main transcript	c.2006C>T	p.Ser669Phe	missense_variant	12/12	1		P1	Q8N5C8-1
TAB3	ENST00000378932.6 linkuse as main transcript	c.1922C>T	p.Ser641Phe	missense_variant	11/11	1			Q8N5C8-2

Frequencies

GnomAD3 genomes

AF:

0.0000808

AC:

AN:

111386

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33558

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

180470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000419

AC:

AN:

1097719

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

363083

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000430

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000694

GnomAD4 genome

AF:

0.0000808

AC:

AN:

111386

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33558

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000247

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

May 25, 2022

The c.2006C>T (p.S669F) alteration is located in exon 11 (coding exon 7) of the TAB3 gene. This alteration results from a C to T substitution at nucleotide position 2006, causing the serine (S) at amino acid position 669 to be replaced by a phenylalanine (F). 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

0.083

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.047

T;T;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

.;T;T

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

0.57

D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.98

N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.014

D;D;T

Sift4G

Uncertain

0.036

D;D;T

Polyphen

0.98

D;D;B

Vest4

0.23

MutPred

0.17

Loss of glycosylation at S669 (P = 0.0095);Loss of glycosylation at S669 (P = 0.0095);.;

MVP

0.45

MPC

0.62

ClinPred

0.10

GERP RS

4.4

Varity_R

0.14

gMVP

0.55

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