X-30854485-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001399870.1(TAB3):​c.1180C>T​(p.Arg394Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,209,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 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. R394R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000068 (0 hom. 23 hem.)
• Consequence: TAB3 NM_001399870.1 missense
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28277123).
• BS2: High Hemizygotes in GnomAdExome4 at 23 gene

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>T	p.Arg394Trp	missense	Exon 6 of 11	NP_690000.3
	TAB3	NM_001399870.1		c.1180C>T	p.Arg394Trp	missense	Exon 6 of 10	NP_001386799.1
	TAB3	NM_001399872.1		c.1180C>T	p.Arg394Trp	missense	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>T	p.Arg394Trp	missense	Exon 6 of 11	ENSP00000288422.4
	TAB3	ENST00000378930.7	TSL:1	c.1180C>T	p.Arg394Trp	missense	Exon 2 of 7	ENSP00000368212.3
	TAB3	ENST00000378933.5	TSL:1	c.1180C>T	p.Arg394Trp	missense	Exon 7 of 12	ENSP00000368215.1

Frequencies

GnomAD3 genomes AF: 0.0000359 AC: 4 AN: 111544 Hom.: 0 Cov.: 22

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: 0.0000754

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000683 AC: 75 AN: 1097819 Hom.: 0 Cov.: 31 AF XY: 0.0000633 AC XY: 23 AN XY: 363199

African (AFR) AF: 0.0000758 AC: 2 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19361

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54076

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.0000832 AC: 70 AN: 841847

Other (OTH) AF: 0.0000434 AC: 2 AN: 46084

GnomAD4 genome AF: 0.0000359 AC: 4 AN: 111544 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33728

African (AFR) AF: 0.00 AC: 0 AN: 30640

American (AMR) AF: 0.00 AC: 0 AN: 10532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6015

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000754 AC: 4 AN: 53065

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.0000318 Hom.: 0

Bravo AF: 0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.28	T
PhyloP100		2.7
Sift4G	Uncertain	0.018	D
Vest4		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5927629; hg19: chrX-30872602;