17-3690982-TGGGG-TGGG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.333delC	p.Asn112ThrfsTer36	frameshift_variant	Exon 3 of 12	ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.333delC	p.Asn112ThrfsTer36	frameshift_variant	Exon 3 of 12	1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.333delC	p.Asn112ThrfsTer36	frameshift_variant	Exon 3 of 13			ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.333delC		non_coding_transcript_exon_variant	Exon 3 of 15	2		ENSP00000455681.1

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

GnomAD3 exomes AF: 0.676 AC: 167917 AN: 248528 Hom.: 59118 AF XY: 0.673 AC XY: 90610 AN XY: 134644

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 SAS exome AF: 0.600

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

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.793

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.811

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.653

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

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.579

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 6808/12518=54.38% -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3215407; hg19: chr17-3594276;