chr17-3664679-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014604.4(TAX1BP3):c.159G>T(p.Lys53Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000116 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TAX1BP3
NM_014604.4 missense, splice_region
NM_014604.4 missense, splice_region
Scores
2
5
7
Splicing: ADA: 0.9995
2
Clinical Significance
Conservation
PhyloP100: 4.47
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAX1BP3 | NM_014604.4 | c.159G>T | p.Lys53Asn | missense_variant, splice_region_variant | 2/4 | ENST00000225525.4 | |
P2RX5-TAX1BP3 | NR_037928.1 | n.5214G>T | splice_region_variant, non_coding_transcript_exon_variant | 13/15 | |||
TAX1BP3 | NM_001204698.2 | c.159G>T | p.Lys53Asn | missense_variant, splice_region_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAX1BP3 | ENST00000225525.4 | c.159G>T | p.Lys53Asn | missense_variant, splice_region_variant | 2/4 | 1 | NM_014604.4 | P1 | |
TAX1BP3 | ENST00000611779.4 | c.159G>T | p.Lys53Asn | missense_variant, splice_region_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250700Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135644
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461488Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727014
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
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33
ExAC
?
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1
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 | May 12, 2023 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with TAX1BP3-related conditions. This variant is present in population databases (rs375177174, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 53 of the TAX1BP3 protein (p.Lys53Asn). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;T
Polyphen
0.26
.;B
Vest4
MutPred
Loss of ubiquitination at K53 (P = 0.0071);Loss of ubiquitination at K53 (P = 0.0071);
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at