12-121165379-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002562.6(P2RX7):​c.556G>A​(p.Glu186Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,613,954 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 2 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

6
6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.768
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
P2RX7NM_002562.6 linkuse as main transcriptc.556G>A p.Glu186Lys missense_variant 6/13 ENST00000328963.10 NP_002553.3
LOC105370032XR_001749352.3 linkuse as main transcriptn.327+38119C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
P2RX7ENST00000328963.10 linkuse as main transcriptc.556G>A p.Glu186Lys missense_variant 6/131 NM_002562.6 ENSP00000330696 P1Q99572-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000835
AC:
21
AN:
251438
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461760
Hom.:
2
Cov.:
30
AF XY:
0.0000839
AC XY:
61
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000487
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.0013
T
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.69
T
REVEL
Uncertain
0.37
Sift4G
Uncertain
0.040
D
Polyphen
1.0
D
Vest4
0.81
MutPred
0.79
Gain of ubiquitination at E186 (P = 0.0592);
MVP
0.76
ClinPred
0.44
T
GERP RS
6.1
Varity_R
0.14
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28360451; hg19: chr12-121603182; COSMIC: COSV55855472; COSMIC: COSV55855472; API