17-3663755-A-G

Position:

chr17-3663755-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014604.4(TAX1BP3):c.368T>C(p.Leu123Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0068 in 1,603,982 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 59 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.50

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:

P2RX5-TAX1BP3 (HGNC:):

P2RX5-TAX1BP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056372285).

BP6

Variant 17-3663755-A-G is Benign according to our data. Variant chr17-3663755-A-G is described in ClinVar as [Benign]. Clinvar id is 2419966.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAX1BP3	NM_014604.4 linkuse as main transcript	c.368T>C	p.Leu123Pro	missense_variant	4/4	ENST00000225525.4	NP_055419.1	O14907
TAX1BP3	NM_001204698.2 linkuse as main transcript	c.290T>C	p.Leu97Pro	missense_variant	3/3		NP_001191627.1	O14907A0A087X282
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.5423T>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAX1BP3	ENST00000225525.4 linkuse as main transcript	c.368T>C	p.Leu123Pro	missense_variant	4/4	1	NM_014604.4	ENSP00000225525.3	O14907
P2RX5-TAX1BP3	ENST00000550383.1 linkuse as main transcript	n.*3725T>C		non_coding_transcript_exon_variant	15/15	2		ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1 linkuse as main transcript	n.*3725T>C		3_prime_UTR_variant	15/15	2		ENSP00000455681.1
TAX1BP3	ENST00000611779.4 linkuse as main transcript	c.290T>C	p.Leu97Pro	missense_variant	3/3	2		ENSP00000484776.1	A0A087X282

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

932

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00664

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00755

AC:

1797

AN:

238046

Hom.:

AF XY:

0.00827

AC XY:

1077

AN XY:

130224

show subpopulations

Gnomad AFR exome

AF:

0.000659

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0152

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.00644

Gnomad OTH exome

AF:

0.00900

GnomAD4 exome

AF:

0.00688

AC:

9981

AN:

1451640

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

5188

AN XY:

722034

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00548

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.00611

Gnomad4 OTH exome

AF:

0.00719

GnomAD4 genome

AF:

0.00613

AC:

934

AN:

152342

Hom.:

Cov.:

AF XY:

0.00664

AC XY:

495

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.00664

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00601

Hom.:

Bravo

AF:

0.00505

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00768

AC:

ExAC

AF:

0.00689

AC:

835

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.00756

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.080

.;N

REVEL

Benign

0.088

Sift

Uncertain

0.0040

.;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.096

.;B

Vest4

0.35

MVP

0.17

MPC

0.82

ClinPred

0.020

GERP RS

5.0

Varity_R

0.34

gMVP

0.61

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