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GeneBe

X-30842988-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152787.5(TAB3):c.1866A>G(p.Val622=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,183,790 control chromosomes in the GnomAD database, including 4 homozygotes. There are 269 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., 129 hem., cov: 23)
Exomes 𝑓: 0.00052 ( 0 hom. 140 hem. )

Consequence

TAB3
NM_152787.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-30842988-T-C is Benign according to our data. Variant chrX-30842988-T-C is described in ClinVar as [Benign]. Clinvar id is 714913.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAB3NM_152787.5 linkuse as main transcriptc.1866A>G p.Val622= synonymous_variant 9/11 ENST00000288422.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAB3ENST00000288422.4 linkuse as main transcriptc.1866A>G p.Val622= synonymous_variant 9/115 NM_152787.5 P1Q8N5C8-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00444
AC:
497
AN:
112022
Hom.:
4
Cov.:
23
AF XY:
0.00375
AC XY:
128
AN XY:
34166
show subpopulations
Gnomad AFR
AF:
0.0153
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00162
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000367
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000939
Gnomad OTH
AF:
0.00264
GnomAD3 exomes
AF:
0.00132
AC:
214
AN:
162457
Hom.:
1
AF XY:
0.000598
AC XY:
30
AN XY:
50155
show subpopulations
Gnomad AFR exome
AF:
0.0160
Gnomad AMR exome
AF:
0.000635
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000691
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000405
Gnomad OTH exome
AF:
0.000508
GnomAD4 exome
AF:
0.000523
AC:
560
AN:
1071717
Hom.:
0
Cov.:
24
AF XY:
0.000409
AC XY:
140
AN XY:
341963
show subpopulations
Gnomad4 AFR exome
AF:
0.0162
Gnomad4 AMR exome
AF:
0.00111
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000607
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.00158
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00445
AC:
499
AN:
112073
Hom.:
4
Cov.:
23
AF XY:
0.00377
AC XY:
129
AN XY:
34227
show subpopulations
Gnomad4 AFR
AF:
0.0153
Gnomad4 AMR
AF:
0.00161
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000369
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000939
Gnomad4 OTH
AF:
0.00261
Alfa
AF:
0.00231
Hom.:
10
Bravo
AF:
0.00515

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
7.3
Dann
Benign
0.71

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs147101613; hg19: chrX-30861105; COSMIC: COSV104385626; API