Variant 17-3690122-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002561.4(P2RX5):c.562T>G(p.Phe188Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

P2RX5
NM_002561.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX5	NM_002561.4 linkuse as main transcript	c.562T>G	p.Phe188Val	missense_variant	6/12	ENST00000225328.10
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.961T>G		non_coding_transcript_exon_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX5	ENST00000225328.10 linkuse as main transcript	c.562T>G	p.Phe188Val	missense_variant	6/12	1	NM_002561.4		Q93086-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.562T>G (p.F188V) alteration is located in exon 6 (coding exon 6) of the P2RX5 gene. This alteration results from a T to G substitution at nucleotide position 562, causing the phenylalanine (F) at amino acid position 188 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

.;.;.;T;.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

3.6

.;.;H;H;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.8

.;D;D;D;D;D

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

.;D;D;D;.;D

Vest4

0.96

MutPred

0.93

Gain of ubiquitination at K193 (P = 0.1162);.;Gain of ubiquitination at K193 (P = 0.1162);Gain of ubiquitination at K193 (P = 0.1162);.;.;

MVP

0.38

MPC

0.70

ClinPred

1.0

GERP RS

5.3

Varity_R

0.91

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

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