X-30831434-T-C

Position:

• chrX-30831434-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152787.5(TAB3):​c.2132A>G​(p.Tyr711Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TAB3 NM_152787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22468567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB3	NM_152787.5	c.2132A>G	p.Tyr711Cys	missense_variant	11/11	ENST00000288422.4
TAB3	NM_001399872.1	c.2048A>G	p.Tyr683Cys	missense_variant	10/10
TAB3	NM_001399873.1	c.2030A>G	p.Tyr677Cys	missense_variant	10/10
TAB3	XM_047441986.1	c.2132A>G	p.Tyr711Cys	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB3	ENST00000288422.4	c.2132A>G	p.Tyr711Cys	missense_variant	11/11	5	NM_152787.5	P1
TAB3	ENST00000378930.7	c.2132A>G	p.Tyr711Cys	missense_variant	7/7	1		P1
TAB3	ENST00000378933.5	c.2132A>G	p.Tyr711Cys	missense_variant	12/12	1		P1
TAB3	ENST00000378932.6	c.2048A>G	p.Tyr683Cys	missense_variant	11/11	1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.2132A>G (p.Y711C) alteration is located in exon 11 (coding exon 7) of the TAB3 gene. This alteration results from a A to G substitution at nucleotide position 2132, causing the tyrosine (Y) at amino acid position 711 to be replaced by a cysteine (C). 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	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	0.78	D;D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.083	T;T;T
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.0060	B;B;P
Vest4		0.29
MutPred		0.51		Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);.;
MVP		0.84
MPC		0.50
ClinPred		0.46	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30849551;