chr17-3663771-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014604.4(TAX1BP3):c.352G>A(p.Val118Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000872 in 1,604,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.85

Variant links:

Genes affected

TAX1BP3 (HGNC:30684): (Tax1 binding protein 3) This gene encodes a small, highly conserved protein with a single PDZ domain. PDZ (PSD-95/Discs large/ZO-1 homologous) domains promote protein-protein interactions that affect cell signaling, adhesion, protein scaffolding, and receptor and ion transporter functions. The encoded protein interacts with a large number of target proteins that play roles in signaling pathways; for example, it interacts with Rho A and glutaminase L and also acts as a negative regulator of the Wnt/beta-catenin signaling pathway. This protein was first identified as binding to the T-cell leukaemia virus (HTLV1) Tax oncoprotein. Overexpression of this gene has been implicated in altered cancer cell adhesion, migration and metastasis. The encoded protein also modulates the localization and density of inwardly rectifying potassium channel 2.3 (Kir2.3). To date, this protein has been shown to play a role in cell proliferation, development, stress response, and polarization. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

TAX1BP3 links:

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103220075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAX1BP3	NM_014604.4 link	c.352G>A	p.Val118Met	missense_variant	Exon 4 of 4	ENST00000225525.4	NP_055419.1	O14907
TAX1BP3	NM_001204698.2 link	c.274G>A	p.Val92Met	missense_variant	Exon 3 of 3		NP_001191627.1	O14907A0A087X282
P2RX5-TAX1BP3	NR_037928.1 link	n.5407G>A		non_coding_transcript_exon_variant	Exon 15 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAX1BP3	ENST00000225525.4 link	c.352G>A	p.Val118Met	missense_variant	Exon 4 of 4	1	NM_014604.4	ENSP00000225525.3	O14907
P2RX5-TAX1BP3	ENST00000550383.1 link	n.*3709G>A		non_coding_transcript_exon_variant	Exon 15 of 15	2		ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1 link	n.*3709G>A		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000455681.1
TAX1BP3	ENST00000611779.4 link	c.274G>A	p.Val92Met	missense_variant	Exon 3 of 3	2		ENSP00000484776.1	A0A087X282

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

238238

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

130340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000506

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000916

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000895

AC:

130

AN:

1452490

Hom.:

Cov.:

AF XY:

0.0000913

AC XY:

AN XY:

722664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000900

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000836

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.352G>A (p.V118M) alteration is located in exon 4 (coding exon 4) of the TAX1BP3 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the valine (V) at amino acid position 118 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Sep 20, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬¨‚Ä†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 2393433). This variant has not been reported in the literature in individuals affected with TAX1BP3-related conditions. This variant is present in population databases (rs201603326, gnomAD 0.05%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 118 of the TAX1BP3 protein (p.Val118Met). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.86

.;N

REVEL

Benign

0.074

Sift

Uncertain

0.0090

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.67

.;P

Vest4

0.46

MVP

0.17

MPC

0.43

ClinPred

0.045

GERP RS

4.1

Varity_R

0.43

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over