NM_002562.6:c.1298C>T

Variant names:

• chr12-121184312-C-T
• rs28360459
• NM_002562.6:c.1298C>T

Variant summary

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

The NM_002562.6(P2RX7):​c.1298C>T​(p.Ala433Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,601,540 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.031 (242 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (243 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 8 publications found

Genes affected

P2RX7 (HGNC:8537): (purinergic receptor P2X 7) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

ENSG00000286248 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015043914).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. 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
	P2RX7	NM_002562.6	MANE Select	c.1298C>T	p.Ala433Val	missense	Exon 13 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1616C>T		non_coding_transcript_exon	Exon 13 of 13
	P2RX7	NR_033949.2		n.1532C>T		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1298C>T	p.Ala433Val	missense	Exon 13 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*751C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1053C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4703 AN: 152152 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00860 AC: 2111 AN: 245556 AF XY: 0.00627

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00565

Gnomad ASJ exome AF: 0.000833

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000430

Gnomad OTH exome AF: 0.00421

GnomAD4 exome AF: 0.00323 AC: 4684 AN: 1449270 Hom.: 243 Cov.: 31 AF XY: 0.00286 AC XY: 2055 AN XY: 719184

African (AFR) AF: 0.111 AC: 3668 AN: 33082

American (AMR) AF: 0.00668 AC: 288 AN: 43122

Ashkenazi Jewish (ASJ) AF: 0.000819 AC: 21 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52938

Middle Eastern (MID) AF: 0.00525 AC: 30 AN: 5712

European-Non Finnish (NFE) AF: 0.000230 AC: 254 AN: 1104272

Other (OTH) AF: 0.00682 AC: 408 AN: 59800

GnomAD4 genome AF: 0.0310 AC: 4723 AN: 152270 Hom.: 242 Cov.: 32 AF XY: 0.0297 AC XY: 2213 AN XY: 74454

African (AFR) AF: 0.108 AC: 4480 AN: 41540

American (AMR) AF: 0.0110 AC: 169 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68018

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.00886 Hom.: 130

Bravo AF: 0.0358

ESP6500AA AF: 0.116 AC: 510

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.0105 AC: 1279

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.8
DANN	Benign	0.63
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.82
PrimateAI	Benign	0.19	T
REVEL	Benign	0.091
Sift4G	Benign	0.25	T
Polyphen		0.0030	B
Vest4		0.023
ClinPred		0.0014	T
GERP RS		-5.1
Varity_R		0.025
gMVP		0.14
Mutation Taster		=99/1	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: rs28360459; hg19: chr12-121622115;