17-3664718-A-G

Position:

• chr17-3664718-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014604.4(TAX1BP3):​c.120T>C​(p.Asp40Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 1,613,640 control chromosomes in the GnomAD database, including 612,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55486 hom., cov: 32)
  • Exomes 𝑓: 0.87 (556670 hom.)
• Consequence: TAX1BP3 NM_014604.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.329

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]

P2RX5-TAX1BP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-3664718-A-G is Benign according to our data. Variant chr17-3664718-A-G is described in ClinVar as [Benign]. Clinvar id is 1577462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAX1BP3	NM_014604.4	c.120T>C	p.Asp40Asp	synonymous_variant	2/4	ENST00000225525.4	NP_055419.1
TAX1BP3	NM_001204698.2	c.120T>C	p.Asp40Asp	synonymous_variant	2/3		NP_001191627.1
P2RX5-TAX1BP3	NR_037928.1	n.5175T>C		non_coding_transcript_exon_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAX1BP3	ENST00000225525.4	c.120T>C	p.Asp40Asp	synonymous_variant	2/4	1	NM_014604.4	ENSP00000225525.3
P2RX5-TAX1BP3	ENST00000550383.1	n.*3477T>C		non_coding_transcript_exon_variant	13/15	2		ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1	n.*3477T>C		3_prime_UTR_variant	13/15	2		ENSP00000455681.1
TAX1BP3	ENST00000611779.4	c.120T>C	p.Asp40Asp	synonymous_variant	2/3	2		ENSP00000484776.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129570 AN: 151994 Hom.: 55468 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.860

GnomAD3 exomes AF: 0.844 AC: 212024 AN: 251212 Hom.: 89978 AF XY: 0.845 AC XY: 114775 AN XY: 135844

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.906

Gnomad EAS exome AF: 0.700

Gnomad SAS exome AF: 0.782

Gnomad FIN exome AF: 0.874

Gnomad NFE exome AF: 0.892

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.872 AC: 1273731 AN: 1461528 Hom.: 556670 Cov.: 57 AF XY: 0.869 AC XY: 632012 AN XY: 727050

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.783

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.854

GnomAD4 genome AF: 0.852 AC: 129630 AN: 152112 Hom.: 55486 Cov.: 32 AF XY: 0.848 AC XY: 63084 AN XY: 74348

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.852

Alfa AF: 0.880 Hom.: 29962

Bravo AF: 0.849

Asia WGS AF: 0.705 AC: 2455 AN: 3478

EpiCase AF: 0.886

EpiControl AF: 0.890

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs8278; hg19: chr17-3568012;