rs8278

Variant names:

• chr17-3664718-A-G
• rs8278
• NM_014604.4:c.120T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-3664718-A-G
• chr17-3664718-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014604.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAX1BP3	NM_014604.4	MANE Select	c.120T>C	p.Asp40Asp	synonymous	Exon 2 of 4	NP_055419.1	O14907
	TAX1BP3	NM_001204698.2		c.120T>C	p.Asp40Asp	synonymous	Exon 2 of 3	NP_001191627.1	A0A087X282
	P2RX5-TAX1BP3	NR_037928.1		n.5175T>C		non_coding_transcript_exon	Exon 13 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAX1BP3	ENST00000225525.4	TSL:1 MANE Select	c.120T>C	p.Asp40Asp	synonymous	Exon 2 of 4	ENSP00000225525.3	O14907
	P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3477T>C		non_coding_transcript_exon	Exon 13 of 15	ENSP00000455681.1
	P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3477T>C		3_prime_UTR	Exon 13 of 15	ENSP00000455681.1

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

GnomAD2 exomes AF: 0.844 AC: 212024 AN: 251212 AF XY: 0.845

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 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

African (AFR) AF: 0.813 AC: 27204 AN: 33476

American (AMR) AF: 0.800 AC: 35796 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 23629 AN: 26134

East Asian (EAS) AF: 0.710 AC: 28173 AN: 39692

South Asian (SAS) AF: 0.783 AC: 67526 AN: 86252

European-Finnish (FIN) AF: 0.871 AC: 46302 AN: 53184

Middle Eastern (MID) AF: 0.820 AC: 4730 AN: 5766

European-Non Finnish (NFE) AF: 0.889 AC: 988772 AN: 1111918

Other (OTH) AF: 0.854 AC: 51599 AN: 60386

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

African (AFR) AF: 0.812 AC: 33681 AN: 41488

American (AMR) AF: 0.842 AC: 12867 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3578 AN: 5160

South Asian (SAS) AF: 0.778 AC: 3748 AN: 4818

European-Finnish (FIN) AF: 0.866 AC: 9171 AN: 10586

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60553 AN: 67986

Other (OTH) AF: 0.852 AC: 1799 AN: 2112

Alfa AF: 0.880 Hom.: 38141

Bravo AF: 0.849

Asia WGS AF: 0.705 AC: 2455 AN: 3478

EpiCase AF: 0.886

EpiControl AF: 0.890

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8278; hg19: chr17-3568012; COSMIC: COSV108016615; COSMIC: COSV108016615;