Variant chr11-57346653-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000263314.3(P2RX3):c.229G>A(p.Val77Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

P2RX3
ENST00000263314.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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:

P2RX3 (HGNC:):

P2RX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX3	NM_002559.5 linkuse as main transcript	c.229G>A	p.Val77Met	missense_variant	2/12	ENST00000263314.3	NP_002550.2	P56373

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX3	ENST00000263314.3 linkuse as main transcript	c.229G>A	p.Val77Met	missense_variant	2/12	1	NM_002559.5	ENSP00000263314.2		P56373

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251368

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135850

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 17, 2023

The c.229G>A (p.V77M) alteration is located in exon 2 (coding exon 2) of the P2RX3 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the valine (V) at amino acid position 77 to be replaced by a methionine (M). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.0099

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.26

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.59

MutPred

0.85

Gain of phosphorylation at T82 (P = 0.0879);Gain of phosphorylation at T82 (P = 0.0879);

MVP

0.79

MPC

0.90

ClinPred

0.97

GERP RS

3.7

Varity_R

0.49

gMVP

0.85

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