chrX-30852842-C-T

Variant names:

• chrX-30852842-C-T
• rs1234023670
• NM_152787.5:c.1646G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152787.5(TAB3):​c.1646G>A​(p.Gly549Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,209,577 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: TAB3 NM_152787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07160336).

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.1646G>A	p.Gly549Asp	missense	Exon 7 of 11	NP_690000.3	Q8N5C8-1
	TAB3	NM_001399870.1		c.1646G>A	p.Gly549Asp	missense	Exon 7 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1646G>A	p.Gly549Asp	missense	Exon 7 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.1646G>A	p.Gly549Asp	missense	Exon 7 of 11	ENSP00000288422.4	Q8N5C8-1
	TAB3	ENST00000378930.7	TSL:1	c.1646G>A	p.Gly549Asp	missense	Exon 3 of 7	ENSP00000368212.3	Q8N5C8-1
	TAB3	ENST00000378933.5	TSL:1	c.1646G>A	p.Gly549Asp	missense	Exon 8 of 12	ENSP00000368215.1	Q8N5C8-1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111755 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183142 AF XY: 0.0000148

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: 0.00000273 AC: 3 AN: 1097822 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363180

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40475

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841816

Other (OTH) AF: 0.00 AC: 0 AN: 46081

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111755 Hom.: 0 Cov.: 24 AF XY: 0.0000295 AC XY: 1 AN XY: 33933

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30746

American (AMR) AF: 0.00 AC: 0 AN: 10479

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3581

South Asian (SAS) AF: 0.00 AC: 0 AN: 2664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53190

Other (OTH) AF: 0.00 AC: 0 AN: 1498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.045	T
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.075
Sift	Benign	0.83	T
Sift4G	Benign	0.88	T
Polyphen		0.030	B
Vest4		0.20
MutPred		0.17		Loss of MoRF binding (P = 0.0679)
MVP		0.63
MPC		0.56
ClinPred		0.13	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.47
Mutation Taster		=289/11	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: rs1234023670; hg19: chrX-30870959;