Variant 17-3679584-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002561.4(P2RX5):c.1259+6G>A variant causes a splice donor 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. 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_donor_region, intron

Scores

Splicing: ADA: 0.00006244

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.366

Variant links:

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 links:

P2RX5-TAX1BP3 (HGNC:):

P2RX5-TAX1BP3 links:

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ACMG classification

Classification made for transcript

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	UniProt
P2RX5	NM_002561.4 linkuse as main transcript	c.1259+6G>A		splice_donor_region_variant, intron_variant		ENST00000225328.10
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.1658+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX5	ENST00000225328.10 linkuse as main transcript	c.1259+6G>A		splice_donor_region_variant, intron_variant		1	NM_002561.4		Q93086-3

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

152186

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00496

AC XY:

661

AN XY:

133234

show subpopulations

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.:

Cov.:

AF XY:

0.00604

AC XY:

4369

AN XY:

723410

show subpopulations

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.:

Cov.:

AF XY:

0.00454

AC XY:

338

AN XY:

74468

show subpopulations

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.:

Bravo

AF:

0.00473

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00856

EpiControl

AF:

0.00771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	P2RX5: BP4, BS2 -

P2RX5-related disorder

Benign:1

Benign, criteria provided, single submitter

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over