rs201603326

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 š‘“: 0.0000028 ( 0 hom. )

Consequence

TAX1BP3
NM_014604.4 missense

Scores

1
5
13

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]
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]

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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=0.16691989).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAX1BP3NM_014604.4 linkc.352G>C p.Val118Leu missense_variant Exon 4 of 4 ENST00000225525.4 NP_055419.1 O14907
TAX1BP3NM_001204698.2 linkc.274G>C p.Val92Leu missense_variant Exon 3 of 3 NP_001191627.1 O14907A0A087X282
P2RX5-TAX1BP3NR_037928.1 linkn.5407G>C non_coding_transcript_exon_variant Exon 15 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAX1BP3ENST00000225525.4 linkc.352G>C p.Val118Leu missense_variant Exon 4 of 4 1 NM_014604.4 ENSP00000225525.3 O14907
P2RX5-TAX1BP3ENST00000550383.1 linkn.*3709G>C non_coding_transcript_exon_variant Exon 15 of 15 2 ENSP00000455681.1
P2RX5-TAX1BP3ENST00000550383.1 linkn.*3709G>C 3_prime_UTR_variant Exon 15 of 15 2 ENSP00000455681.1
TAX1BP3ENST00000611779.4 linkc.274G>C p.Val92Leu missense_variant Exon 3 of 3 2 ENSP00000484776.1 A0A087X282

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000839
AC:
2
AN:
238238
Hom.:
0
AF XY:
0.00000767
AC XY:
1
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:
4
AN:
1452492
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
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.:
33
ExAC
AF:
0.0000165
AC:
2

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
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
.;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.036
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;L
PrimateAI
Uncertain
0.72
T
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
T
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.

Other links and lift over

dbSNP: rs201603326; hg19: chr17-3567065; API