rs771530217

Variant names:

• chrX-30852787-C-A
• rs771530217
• NM_152787.5:c.1701G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-30852787-C-A
• chrX-30852787-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_152787.5(TAB3):​c.1701G>T​(p.Ala567Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,208,426 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A567A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: TAB3 NM_152787.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-2.87 with no splicing effect.
• 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.1701G>T	p.Ala567Ala	synonymous	Exon 7 of 11	NP_690000.3	Q8N5C8-1
	TAB3	NM_001399870.1		c.1701G>T	p.Ala567Ala	synonymous	Exon 7 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1701G>T	p.Ala567Ala	synonymous	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.1701G>T	p.Ala567Ala	synonymous	Exon 7 of 11	ENSP00000288422.4	Q8N5C8-1
	TAB3	ENST00000378930.7	TSL:1	c.1701G>T	p.Ala567Ala	synonymous	Exon 3 of 7	ENSP00000368212.3	Q8N5C8-1
	TAB3	ENST00000378933.5	TSL:1	c.1701G>T	p.Ala567Ala	synonymous	Exon 8 of 12	ENSP00000368215.1	Q8N5C8-1

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111643 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000977

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181638 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: 0.00

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1096732 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 2 AN XY: 362178

African (AFR) AF: 0.000152 AC: 4 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 35164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19344

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 53849

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841423

Other (OTH) AF: 0.0000434 AC: 2 AN: 46045

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111694 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33872

African (AFR) AF: 0.0000975 AC: 3 AN: 30774

American (AMR) AF: 0.00 AC: 0 AN: 10487

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53145

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.39
DANN	Benign	0.83
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs771530217; hg19: chrX-30870904;