Variant 11-57368071-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002559.5(P2RX3):c.905G>T(p.Gly302Val) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

P2RX3
NM_002559.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

P2RX3 (HGNC:8534): (purinergic receptor P2X 3) This gene encodes a member of the P2X purinergic receptor (purinoceptor) gene family which includes seven members (P2RX1 - P2RX7). P2X purinoceptors are a family of cation-permeable, ligand-gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate (ATP). The encoded protein is a subunit of the trimeric P2X3 receptor ion channel which is expressed by sensory or autonomic neurons. A deficiency of the orthologous protein in mice is associated with reduced pain-related behavior and urinary bladder hyporeflexia. [provided by RefSeq, Aug 2017]

P2RX3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34192276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX3	NM_002559.5 linkuse as main transcript	c.905G>T	p.Gly302Val	missense_variant	9/12	ENST00000263314.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX3	ENST00000263314.3 linkuse as main transcript	c.905G>T	p.Gly302Val	missense_variant	9/12	1	NM_002559.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

251458

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00124

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152268

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000552

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

Aug 19, 2021

The c.905G>T (p.G302V) alteration is located in exon 9 (coding exon 9) of the P2RX3 gene. This alteration results from a G to T substitution at nucleotide position 905, causing the glycine (G) at amino acid position 302 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

0.98

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.040

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.95

.;P

Vest4

0.80

MVP

0.82

MPC

0.96

ClinPred

0.44

GERP RS

6.1

Varity_R

0.93

gMVP

0.98

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