NM_002562.6:c.1289C>G

Variant names:

• chr12-121180454-C-G
• rs10160951
• NM_002562.6:c.1289C>G

Variant summary

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

The NM_002562.6(P2RX7):​c.1289C>G​(p.Pro430Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,517,598 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P430T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.042 (408 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (404 hom.)
• Consequence: P2RX7 NM_002562.6 missense, splice_region
• Scores: Splicing: ADA: 0.05033
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 12 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=0.0018902719).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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.1289C>G	p.Pro430Arg	missense splice_region	Exon 12 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1607C>G		splice_region non_coding_transcript_exon	Exon 12 of 13
	P2RX7	NR_033949.2		n.1523C>G		splice_region non_coding_transcript_exon	Exon 13 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1289C>G	p.Pro430Arg	missense splice_region	Exon 12 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*742C>G		splice_region non_coding_transcript_exon	Exon 11 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1044C>G		splice_region non_coding_transcript_exon	Exon 13 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6380 AN: 151036 Hom.: 409 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0352

GnomAD2 exomes AF: 0.0136 AC: 2930 AN: 215124 AF XY: 0.0103

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00275

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00240

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.00568 AC: 7755 AN: 1366464 Hom.: 404 Cov.: 22 AF XY: 0.00516 AC XY: 3524 AN XY: 683250

African (AFR) AF: 0.152 AC: 4506 AN: 29612

American (AMR) AF: 0.0139 AC: 458 AN: 33062

Ashkenazi Jewish (ASJ) AF: 0.00274 AC: 66 AN: 24080

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.000924 AC: 72 AN: 77892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52450

Middle Eastern (MID) AF: 0.0451 AC: 246 AN: 5458

European-Non Finnish (NFE) AF: 0.00157 AC: 1650 AN: 1048330

Other (OTH) AF: 0.0134 AC: 757 AN: 56584

GnomAD4 genome AF: 0.0423 AC: 6387 AN: 151134 Hom.: 408 Cov.: 31 AF XY: 0.0399 AC XY: 2943 AN XY: 73766

African (AFR) AF: 0.141 AC: 5814 AN: 41186

American (AMR) AF: 0.0209 AC: 317 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000419 AC: 2 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10240

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 67856

Other (OTH) AF: 0.0348 AC: 73 AN: 2096

Alfa AF: 0.00833 Hom.: 57

Bravo AF: 0.0483

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.138 AC: 607

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.0145 AC: 1765

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.0
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.078
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.80
PrimateAI	Benign	0.31	T
REVEL	Benign	0.12
Sift4G	Benign	0.26	T
Polyphen		0.26	B
Vest4		0.081
ClinPred		0.013	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.23
Mutation Taster		=66/34	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.050
dbscSNV1_RF	Benign	0.37
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

Other links and lift over

dbSNP: rs10160951; hg19: chr12-121618257;