rs25644

Variant names:

• chr12-121228843-A-G
• rs25644
• NM_002560.3:c.724A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-121228843-A-G
• chr12-121228843-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002560.3(P2RX4):​c.724A>G​(p.Ser242Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,984 control chromosomes in the GnomAD database, including 15,283 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1593 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13690 hom.)
• Consequence: P2RX4 NM_002560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 38 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076737404).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002560.3. 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
	P2RX4	NM_002560.3	MANE Select	c.724A>G	p.Ser242Gly	missense	Exon 7 of 12	NP_002551.2
	P2RX4	NM_001256796.2		c.772A>G	p.Ser258Gly	missense	Exon 8 of 13	NP_001243725.1	Q99571-2
	P2RX4	NM_001261397.2		c.643A>G	p.Ser215Gly	missense	Exon 7 of 12	NP_001248326.1	Q99571-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX4	ENST00000337233.9	TSL:1 MANE Select	c.724A>G	p.Ser242Gly	missense	Exon 7 of 12	ENSP00000336607.4	Q99571-1
	P2RX4	ENST00000542067.5	TSL:1	c.643A>G	p.Ser215Gly	missense	Exon 7 of 12	ENSP00000438329.1	Q99571-3
	P2RX4	ENST00000543318.5	TSL:1	n.*315A>G		non_coding_transcript_exon	Exon 8 of 13	ENSP00000444274.1	F5GZQ9

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20570 AN: 152012 Hom.: 1584 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.166 AC: 41653 AN: 251448 AF XY: 0.159

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.240

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.129 AC: 187985 AN: 1461854 Hom.: 13690 Cov.: 34 AF XY: 0.128 AC XY: 93371 AN XY: 727230

African (AFR) AF: 0.114 AC: 3818 AN: 33476

American (AMR) AF: 0.321 AC: 14338 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3158 AN: 26136

East Asian (EAS) AF: 0.209 AC: 8301 AN: 39698

South Asian (SAS) AF: 0.163 AC: 14027 AN: 86258

European-Finnish (FIN) AF: 0.164 AC: 8770 AN: 53418

Middle Eastern (MID) AF: 0.124 AC: 714 AN: 5768

European-Non Finnish (NFE) AF: 0.114 AC: 126618 AN: 1111980

Other (OTH) AF: 0.136 AC: 8241 AN: 60396

GnomAD4 genome AF: 0.135 AC: 20596 AN: 152130 Hom.: 1593 Cov.: 31 AF XY: 0.140 AC XY: 10402 AN XY: 74378

African (AFR) AF: 0.121 AC: 5029 AN: 41526

American (AMR) AF: 0.211 AC: 3228 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 414 AN: 3462

East Asian (EAS) AF: 0.228 AC: 1177 AN: 5162

South Asian (SAS) AF: 0.179 AC: 862 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10582

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7796 AN: 67990

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.125 Hom.: 4008

Bravo AF: 0.141

TwinsUK AF: 0.122 AC: 453

ALSPAC AF: 0.115 AC: 442

ESP6500AA AF: 0.120 AC: 529

ESP6500EA AF: 0.118 AC: 1016

ExAC AF: 0.157 AC: 19011

Asia WGS AF: 0.207 AC: 718 AN: 3478

EpiCase AF: 0.110

EpiControl AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.0016
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.023	D
Polyphen		0.087	B
Vest4		0.099
MPC		0.41
ClinPred		0.030	T
GERP RS		5.3
Varity_R		0.27
gMVP		0.66
Mutation Taster		=74/26	polymorphism (auto)

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

Other links and lift over

dbSNP: rs25644; hg19: chr12-121666646; COSMIC: COSV61502287; COSMIC: COSV61502287;