12-121165379-G-A
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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
NM_002562.6 missense
Scores
6
6
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.12
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]
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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 |
---|---|---|---|---|---|---|---|---|
P2RX7 | NM_002562.6 | c.556G>A | p.Glu186Lys | missense_variant | 6/13 | ENST00000328963.10 | NP_002553.3 | |
LOC105370032 | XR_001749352.3 | n.327+38119C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
P2RX7 | ENST00000328963.10 | c.556G>A | p.Glu186Lys | missense_variant | 6/13 | 1 | NM_002562.6 | ENSP00000330696 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251438Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135886
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GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461760Hom.: 2 Cov.: 30 AF XY: 0.0000839 AC XY: 61AN XY: 727184
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74400
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at E186 (P = 0.0592);
MVP
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at