X-30854485-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152787.5(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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000068 ( 0 hom. 23 hem. )

Consequence

TAB3
NM_152787.5 missense

Scores

3
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.73
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAB3NM_152787.5 linkuse as main transcriptc.1180C>T p.Arg394Trp missense_variant 6/11 ENST00000288422.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAB3ENST00000288422.4 linkuse as main transcriptc.1180C>T p.Arg394Trp missense_variant 6/115 NM_152787.5 P1Q8N5C8-1
TAB3-AS2ENST00000445240.1 linkuse as main transcriptn.70G>A non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
AF:
0.0000359
AC:
4
AN:
111544
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33728
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0000758
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.0000832
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000359
AC:
4
AN:
111544
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33728
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000754
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000359
Hom.:
0
Bravo
AF:
0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
25
LIST_S2
Uncertain
0.96
.;D;D
MetaRNN
Benign
0.28
T;T;T
Sift4G
Uncertain
0.018
D;D;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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5927629; hg19: chrX-30872602; API