X-30854790-T-C

Position:

• chrX-30854790-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.875A>G​(p.Tyr292Cys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: TAB3 NM_152787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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=0.24285164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB3	NM_152787.5	c.875A>G	p.Tyr292Cys	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	c.875A>G	p.Tyr292Cys	missense_variant	6/11	5	NM_152787.5	ENSP00000288422.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

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

Jul 10, 2024

The c.875A>G (p.Y292C) alteration is located in exon 6 (coding exon 2) of the TAB3 gene. This alteration results from a A to G substitution at nucleotide position 875, causing the tyrosine (Y) at amino acid position 292 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	0.13
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T;T;.
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.74	N;N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.096	T;T;T
Polyphen		0.97	D;D;D
Vest4		0.34
MutPred		0.23		Loss of phosphorylation at Y292 (P = 0.0038);Loss of phosphorylation at Y292 (P = 0.0038);Loss of phosphorylation at Y292 (P = 0.0038);
MVP		0.46
MPC		1.1
ClinPred		0.86	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30872907;