chrX-30854311-T-C

Variant names:

• chrX-30854311-T-C
• rs1938978715
• NM_152787.5:c.1354A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_152787.5(TAB3):​c.1354A>G​(p.Thr452Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,097,889 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: TAB3 NM_152787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09184718).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB3	NM_152787.5	MANE Select	c.1354A>G	p.Thr452Ala	missense	Exon 6 of 11	NP_690000.3	Q8N5C8-1
	TAB3	NM_001399870.1		c.1354A>G	p.Thr452Ala	missense	Exon 6 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1354A>G	p.Thr452Ala	missense	Exon 6 of 10	NP_001386801.1	Q8N5C8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB3	ENST00000288422.4	TSL:5 MANE Select	c.1354A>G	p.Thr452Ala	missense	Exon 6 of 11	ENSP00000288422.4	Q8N5C8-1
	TAB3	ENST00000378930.7	TSL:1	c.1354A>G	p.Thr452Ala	missense	Exon 2 of 7	ENSP00000368212.3	Q8N5C8-1
	TAB3	ENST00000378933.5	TSL:1	c.1354A>G	p.Thr452Ala	missense	Exon 7 of 12	ENSP00000368215.1	Q8N5C8-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097889 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363253

African (AFR) AF: 0.00 AC: 0 AN: 26385

American (AMR) AF: 0.00 AC: 0 AN: 35170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19368

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54089

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841941

Other (OTH) AF: 0.00 AC: 0 AN: 46078

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.11
Sift	Benign	0.25	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.19		Loss of glycosylation at T452 (P = 0.0047)
MVP		0.64
MPC		0.41
ClinPred		0.44	T
GERP RS		3.7
Varity_R		0.14
gMVP		0.57
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1938978715; hg19: chrX-30872428;