Variant 12-121210171-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002560.3(P2RX4):c.7G>T(p.Gly3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,521,404 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 26 hom. )

Consequence

P2RX4
NM_002560.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.104

Variant links:

Genes affected

P2RX4 (HGNC:8535): (purinergic receptor P2X 4) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with high calcium permeability. The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists suramin and PPADS. The product of this gene has the lowest sensitivity for these antagonists. Multiple alternatively spliced transcript variants, some protein-coding and some not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

P2RX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008266151).

BP6

Variant 12-121210171-G-T is Benign according to our data. Variant chr12-121210171-G-T is described in ClinVar as [Benign]. Clinvar id is 773550.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX4	NM_002560.3 link	c.7G>T	p.Gly3Cys	missense_variant	1/12	ENST00000337233.9	NP_002551.2	Q99571-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX4	ENST00000337233.9 link	c.7G>T	p.Gly3Cys	missense_variant	1/12	1	NM_002560.3	ENSP00000336607.4		Q99571-1

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

635

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00596

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00599

AC:

804

AN:

134224

Hom.:

AF XY:

0.00572

AC XY:

434

AN XY:

75822

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.000976

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.00809

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00522

AC:

7142

AN:

1369218

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

3498

AN XY:

678014

show subpopulations

Gnomad4 AFR exome

AF:

0.000711

Gnomad4 AMR exome

AF:

0.000944

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000784

Gnomad4 FIN exome

AF:

0.0156

Gnomad4 NFE exome

AF:

0.00572

Gnomad4 OTH exome

AF:

0.00393

GnomAD4 genome

AF:

0.00417

AC:

635

AN:

152186

Hom.:

Cov.:

AF XY:

0.00456

AC XY:

339

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.00596

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00459

Hom.:

Bravo

AF:

0.00305

ESP6500AA

AF:

0.000495

AC:

ESP6500EA

AF:

0.00548

AC:

ExAC

AF:

0.00436

AC:

498

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

D;T;.;.;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.76

T;T;T;T;T

MetaRNN

Benign

0.0083

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M;.;M

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.2

D;.;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;.;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

D;.;.;.;.

Vest4

0.14

MVP

0.65

MPC

1.1

ClinPred

0.034

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.60

gMVP

0.66

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