chr12-121156127-G-A

Variant names:

• chr12-121156127-G-A
• rs1878525339
• NM_002562.6:c.343G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002562.6(P2RX7):​c.343G>A​(p.Glu115Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122
• Publications: 0 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]

LOC105370032 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12598404).

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.343G>A	p.Glu115Lys	missense	Exon 3 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.577G>A		non_coding_transcript_exon	Exon 4 of 13
	P2RX7	NR_033949.2		n.577G>A		non_coding_transcript_exon	Exon 4 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.343G>A	p.Glu115Lys	missense	Exon 3 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.343G>A		non_coding_transcript_exon	Exon 3 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*98G>A		non_coding_transcript_exon	Exon 4 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.2
DANN	Benign	0.95
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.12
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.89	T
Polyphen		0.0030	B
Vest4		0.22
MutPred		0.45		Gain of ubiquitination at E115 (P = 0.0211)
MVP		0.30
ClinPred		0.15	T
GERP RS		0.55
Varity_R		0.027
gMVP		0.38
Mutation Taster		=96/4	polymorphism

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: rs1878525339; hg19: chr12-121593930;