12-121167552-G-C

Position:

• chr12-121167552-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002562.6(P2RX7):​c.809G>C​(p.Arg270Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R270C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

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]

LOC105370032 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.809G>C	p.Arg270Pro	missense_variant	8/13	ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+35946C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.809G>C	p.Arg270Pro	missense_variant	8/13	1	NM_002562.6	ENSP00000330696	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250430 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135410

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.28	T
REVEL	Benign	0.17
Sift4G	Benign	0.28	T
Polyphen		0.89	P
Vest4		0.52
MutPred		0.55		Loss of MoRF binding (P = 0.0079);
MVP		0.70
ClinPred		0.77	D
GERP RS		0.97
Varity_R		0.26
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs7958311; hg19: chr12-121605355;