chr17-3679584-C-T

Position:

• chr17-3679584-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002561.4(P2RX5):​c.1259+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,605,840 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (37 hom.)
• Consequence: P2RX5 NM_002561.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006244
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.366

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]

P2RX5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-3679584-C-T is Benign according to our data. Variant chr17-3679584-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1242253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.1259+6G>A		splice_region_variant, intron_variant		ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.1259+6G>A		splice_region_variant, intron_variant		1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.1325+6G>A		splice_region_variant, intron_variant				ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.1259+6G>A		splice_region_variant, intron_variant		2		ENSP00000455681.1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152186 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00469 AC: 1151 AN: 245364 Hom.: 3 AF XY: 0.00496 AC XY: 661 AN XY: 133234

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00504

Gnomad NFE exome AF: 0.00607

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00625 AC: 9089 AN: 1453536 Hom.: 37 Cov.: 32 AF XY: 0.00604 AC XY: 4369 AN XY: 723410

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00437

Gnomad4 NFE exome AF: 0.00693

Gnomad4 OTH exome AF: 0.00693

GnomAD4 genome AF: 0.00469 AC: 714 AN: 152304 Hom.: 3 Cov.: 33 AF XY: 0.00454 AC XY: 338 AN XY: 74468

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00508

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00541 Hom.: 0

Bravo AF: 0.00473

Asia WGS AF: 0.000577 AC: 3 AN: 3478

EpiCase AF: 0.00856

EpiControl AF: 0.00771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	P2RX5: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

P2RX5-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000062
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		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: rs185353702; hg19: chr17-3582878;