Variant 11-57348212-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002559.5(P2RX3):c.434G>A(p.Arg145Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,602,536 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R145W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 9 hom. )

Consequence

P2RX3
NM_002559.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009475559).

BP6

Variant 11-57348212-G-A is Benign according to our data. Variant chr11-57348212-G-A is described in ClinVar as [Benign]. Clinvar id is 717349.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00065 (943/1450228) while in subpopulation AFR AF= 0.0175 (582/33348). AF 95% confidence interval is 0.0163. There are 9 homozygotes in gnomad4_exome. There are 406 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX3	NM_002559.5 linkuse as main transcript	c.434G>A	p.Arg145Gln	missense_variant	5/12	ENST00000263314.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX3	ENST00000263314.3 linkuse as main transcript	c.434G>A	p.Arg145Gln	missense_variant	5/12	1	NM_002559.5	P1
P2RX3	ENST00000534820.1 linkuse as main transcript	c.98G>A	p.Arg33Gln	missense_variant, NMD_transcript_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

745

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00152

AC:

349

AN:

229886

Hom.:

AF XY:

0.00110

AC XY:

136

AN XY:

123688

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.000650

AC:

943

AN:

1450228

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

406

AN XY:

719990

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.0000775

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.0000479

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.00183

GnomAD4 genome

AF:

0.00488

AC:

744

AN:

152308

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000935

Hom.:

Bravo

AF:

0.00591

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00157

AC:

190

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

Sift4G

Benign

0.11

T;T

Polyphen

0.51

.;P

Vest4

0.27

MVP

0.47

MPC

0.30

ClinPred

0.0067

GERP RS

0.74

Varity_R

0.22

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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