X-30854485-G-T

Variant names:

• chrX-30854485-G-T
• rs5927629
• NM_152787.5:c.1180C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001399870.1(TAB3):​c.1180C>A​(p.Arg394Arg) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. R394R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: TAB3 NM_001399870.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 22 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399870.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB3	NM_152787.5	MANE Select	c.1180C>A	p.Arg394Arg	synonymous	Exon 6 of 11	NP_690000.3
	TAB3	NM_001399870.1		c.1180C>A	p.Arg394Arg	synonymous	Exon 6 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1180C>A	p.Arg394Arg	synonymous	Exon 6 of 10	NP_001386801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB3	ENST00000288422.4	TSL:5 MANE Select	c.1180C>A	p.Arg394Arg	synonymous	Exon 6 of 11	ENSP00000288422.4
	TAB3	ENST00000378930.7	TSL:1	c.1180C>A	p.Arg394Arg	synonymous	Exon 2 of 7	ENSP00000368212.3
	TAB3	ENST00000378933.5	TSL:1	c.1180C>A	p.Arg394Arg	synonymous	Exon 7 of 12	ENSP00000368215.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
PhyloP100		2.7

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: rs5927629; hg19: chrX-30872602;