17-3663794-G-A

Position:

chr17-3663794-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014604.4(TAX1BP3):c.329C>T(p.Thr110Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,607,552 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4045513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TAX1BP3	NM_014604.4 linkuse as main transcript	c.329C>T	p.Thr110Met	missense_variant	4/4	ENST00000225525.4
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.5384C>T		non_coding_transcript_exon_variant	15/15
TAX1BP3	NM_001204698.2 linkuse as main transcript	c.251C>T	p.Thr84Met	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAX1BP3	ENST00000225525.4 linkuse as main transcript	c.329C>T	p.Thr110Met	missense_variant	4/4	1	NM_014604.4	P1
TAX1BP3	ENST00000611779.4 linkuse as main transcript	c.251C>T	p.Thr84Met	missense_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243504

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132758

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000419

AC:

AN:

1455334

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

724130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jul 07, 2023

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This variant has not been reported in the literature in individuals affected with TAX1BP3-related conditions. This variant is present in population databases (rs772867295, gnomAD 0.004%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 110 of the TAX1BP3 protein (p.Thr110Met). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

Sift4G

Benign

0.17

T;T

Polyphen

0.95

.;P

Vest4

0.61

MutPred

0.36

.;Gain of phosphorylation at S113 (P = 0.1998);

MVP

0.32

MPC

1.3

ClinPred

0.37

GERP RS

4.1

Varity_R

0.19

gMVP

0.39

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