dbSNP rs201603326: TAX1BP3:p.Val118Leu (chr17-3663771-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_014604.4(TAX1BP3):c.352G>C(p.Val118Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V118M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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=0.16691989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAX1BP3	NM_014604.4 link	c.352G>C	p.Val118Leu	missense_variant	Exon 4 of 4	ENST00000225525.4	NP_055419.1	O14907
TAX1BP3	NM_001204698.2 link	c.274G>C	p.Val92Leu	missense_variant	Exon 3 of 3		NP_001191627.1	O14907A0A087X282
P2RX5-TAX1BP3	NR_037928.1 link	n.5407G>C		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>C	p.Val118Leu	missense_variant	Exon 4 of 4	1	NM_014604.4	ENSP00000225525.3	O14907
P2RX5-TAX1BP3	ENST00000550383.1 link	n.*3709G>C		non_coding_transcript_exon_variant	Exon 15 of 15	2		ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1 link	n.*3709G>C		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000455681.1
TAX1BP3	ENST00000611779.4 link	c.274G>C	p.Val92Leu	missense_variant	Exon 3 of 3	2		ENSP00000484776.1	A0A087X282

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000839

AC:

AN:

238238

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452492

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722666

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

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

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.93

.;N

REVEL

Benign

0.089

Sift

Uncertain

0.029

.;D

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.0

.;B

Vest4

0.68

MutPred

0.34

.;Loss of catalytic residue at V118 (P = 0.0091);

MVP

0.14

MPC

0.41

ClinPred

0.22

GERP RS

4.1

Varity_R

0.52

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over