17-3690982-TGGGG-TGGG

Variant names:

• chr17-3690982-TG-T
• rs3215407
• NM_002561.4:c.333delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002561.4(P2RX5):​c.333delC​(p.Asn112ThrfsTer36) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.58 (28350 hom., cov: 0)
  • Exomes 𝑓: 0.68 (345742 hom.)
• Consequence: P2RX5 NM_002561.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370
• Publications: 30 publications found

Genes affected

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

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 -10 ACMG points.

• BP6: Variant 17-3690982-TG-T is Benign according to our data. Variant chr17-3690982-TG-T is described in ClinVar as Benign. ClinVar VariationId is 403283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002561.4. 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
	P2RX5	NM_002561.4	MANE Select	c.333delC	p.Asn112ThrfsTer36	frameshift	Exon 3 of 12	NP_002552.2
	P2RX5	NM_001204519.2		c.333delC	p.Asn112ThrfsTer36	frameshift	Exon 3 of 12	NP_001191448.1	Q93086-1
	P2RX5	NM_001425082.1		c.-292delC		5_prime_UTR	Exon 6 of 15	NP_001412011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX5	ENST00000225328.10	TSL:1 MANE Select	c.333delC	p.Asn112ThrfsTer36	frameshift	Exon 3 of 12	ENSP00000225328.5	Q93086-3
	P2RX5	ENST00000697413.1		c.333delC	p.Asn112ThrfsTer36	frameshift	Exon 3 of 13	ENSP00000513301.1	Q93086-6
	P2RX5	ENST00000547178.5	TSL:1	c.333delC	p.Asn112ThrfsTer36	frameshift	Exon 3 of 12	ENSP00000448355.1	Q93086-1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87617 AN: 151856 Hom.: 28342 Cov.: 0

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.676 AC: 167917 AN: 248528 AF XY: 0.673

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.807

Gnomad ASJ exome AF: 0.584

Gnomad EAS exome AF: 0.813

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.682 AC: 996324 AN: 1459892 Hom.: 345742 Cov.: 0 AF XY: 0.680 AC XY: 494003 AN XY: 726174

African (AFR) AF: 0.238 AC: 7972 AN: 33464

American (AMR) AF: 0.793 AC: 35322 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 15175 AN: 26090

East Asian (EAS) AF: 0.811 AC: 32202 AN: 39688

South Asian (SAS) AF: 0.603 AC: 51912 AN: 86086

European-Finnish (FIN) AF: 0.727 AC: 38431 AN: 52858

Middle Eastern (MID) AF: 0.518 AC: 2985 AN: 5762

European-Non Finnish (NFE) AF: 0.696 AC: 772902 AN: 1111056

Other (OTH) AF: 0.653 AC: 39423 AN: 60354

GnomAD4 genome AF: 0.577 AC: 87654 AN: 151974 Hom.: 28350 Cov.: 0 AF XY: 0.581 AC XY: 43137 AN XY: 74280

African (AFR) AF: 0.261 AC: 10824 AN: 41464

American (AMR) AF: 0.716 AC: 10930 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2021 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4176 AN: 5132

South Asian (SAS) AF: 0.598 AC: 2874 AN: 4804

European-Finnish (FIN) AF: 0.725 AC: 7663 AN: 10572

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47283 AN: 67956

Other (OTH) AF: 0.579 AC: 1220 AN: 2108

Alfa AF: 0.571 Hom.: 3610

Bravo AF: 0.563

Asia WGS AF: 0.639 AC: 2218 AN: 3476

EpiCase AF: 0.679

EpiControl AF: 0.678

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.037
Mutation Taster		=166/34	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3215407; hg19: chr17-3594276; COSMIC: COSV56590478; COSMIC: COSV56590478;