rs115850675

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 14/21 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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0200

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 717349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 406 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX3	NM_002559.5	MANE Select	c.434G>A	p.Arg145Gln	missense	Exon 5 of 12	NP_002550.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX3	ENST00000263314.3	TSL:1 MANE Select	c.434G>A	p.Arg145Gln	missense	Exon 5 of 12	ENSP00000263314.2	P56373
P2RX3	ENST00000946171.1		c.434G>A	p.Arg145Gln	missense	Exon 5 of 12	ENSP00000616230.1
P2RX3	ENST00000892409.1		c.428G>A	p.Arg143Gln	missense	Exon 5 of 12	ENSP00000562468.1

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

GnomAD2 exomes

AF:

0.00152

AC:

349

AN:

229886

AF XY:

0.00110

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 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

African (AFR)

AF:

0.0175

AC:

582

AN:

33348

American (AMR)

AF:

0.00189

AC:

AN:

42946

Ashkenazi Jewish (ASJ)

AF:

0.0000775

AC:

AN:

25820

East Asian (EAS)

AF:

0.0000762

AC:

AN:

39354

South Asian (SAS)

AF:

0.0000479

AC:

AN:

83566

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52578

Middle Eastern (MID)

AF:

0.00193

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000135

AC:

149

AN:

1106908

Other (OTH)

AF:

0.00183

AC:

110

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00488

AC:

744

AN:

152308

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0158

AC:

655

AN:

41562

American (AMR)

AF:

0.00353

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00116

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

-0.020

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.046

Sift

Uncertain

0.020

Sift4G

Benign

0.11

Polyphen

0.51

Vest4

0.27

MVP

0.47

MPC

0.30

ClinPred

0.0067

GERP RS

0.74

Varity_R

0.22

gMVP

0.72

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over