17-3668493-C-A

Variant summary

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

The NM_014604.4(TAX1BP3):c.34G>T(p.Val12Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,609,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:):

P2RX5-TAX1BP3 links:

Genome browser will be placed here

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=0.13616547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAX1BP3	NM_014604.4 linkuse as main transcript	c.34G>T	p.Val12Leu	missense_variant	1/4	ENST00000225525.4
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.5094+565G>T		intron_variant, non_coding_transcript_variant
TAX1BP3	NM_001204698.2 linkuse as main transcript	c.34G>T	p.Val12Leu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAX1BP3	ENST00000225525.4 linkuse as main transcript	c.34G>T	p.Val12Leu	missense_variant	1/4	1	NM_014604.4	P1
TAX1BP3	ENST00000611779.4 linkuse as main transcript	c.34G>T	p.Val12Leu	missense_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457642

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.34G>T (p.V12L) alteration is located in exon 1 (coding exon 1) of the TAX1BP3 gene. This alteration results from a G to T substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

Sift4G

Benign

0.81

T;T

Polyphen

0.0

.;B

Vest4

0.52

MutPred

0.38

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.25

MPC

0.41

ClinPred

0.87

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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