rs755675535

Variant names:

• chrX-30854305-C-A
• rs755675535
• NM_152787.5:c.1360G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-30854305-C-A
• chrX-30854305-C-T

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.1360G>T​(p.Val454Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000911 in 1,097,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 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)
  • Exomes 𝑓: 0.0000091 (0 hom. 4 hem.)
• Consequence: TAB3 NM_152787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• 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=0.23307636).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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.1360G>T	p.Val454Phe	missense	Exon 6 of 11	NP_690000.3	Q8N5C8-1
	TAB3	NM_001399870.1		c.1360G>T	p.Val454Phe	missense	Exon 6 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1360G>T	p.Val454Phe	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.1360G>T	p.Val454Phe	missense	Exon 6 of 11	ENSP00000288422.4	Q8N5C8-1
	TAB3	ENST00000378930.7	TSL:1	c.1360G>T	p.Val454Phe	missense	Exon 2 of 7	ENSP00000368212.3	Q8N5C8-1
	TAB3	ENST00000378933.5	TSL:1	c.1360G>T	p.Val454Phe	missense	Exon 7 of 12	ENSP00000368215.1	Q8N5C8-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000245

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1097928 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4 AN XY: 363292

African (AFR) AF: 0.00 AC: 0 AN: 26389

American (AMR) AF: 0.00 AC: 0 AN: 35167

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19366

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

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

European-Non Finnish (NFE) AF: 0.0000119 AC: 10 AN: 842006

Other (OTH) AF: 0.00 AC: 0 AN: 46086

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.25
Sift	Benign	0.11	T
Sift4G	Benign	0.080	T
Polyphen		0.62	P
Vest4		0.39
MutPred		0.38		Gain of ubiquitination at K456 (P = 0.1047)
MVP		0.68
MPC		0.70
ClinPred		0.31	T
GERP RS		4.8
Varity_R		0.42
gMVP		0.76
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs755675535; hg19: chrX-30872422;