17-3690095-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002561.4(P2RX5):c.589C>T(p.Arg197Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
P2RX5
NM_002561.4 missense
NM_002561.4 missense
Scores
5
9
Clinical Significance
Conservation
PhyloP100: 3.13
Genes affected
P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32930773).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RX5 | NM_002561.4 | c.589C>T | p.Arg197Cys | missense_variant | 6/12 | ENST00000225328.10 | |
P2RX5-TAX1BP3 | NR_037928.1 | n.988C>T | non_coding_transcript_exon_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RX5 | ENST00000225328.10 | c.589C>T | p.Arg197Cys | missense_variant | 6/12 | 1 | NM_002561.4 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152224Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000103 AC: 26AN: 251494Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135922
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GnomAD4 exome AF: 0.000129 AC: 188AN: 1461814Hom.: 1 Cov.: 33 AF XY: 0.000129 AC XY: 94AN XY: 727204
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152342Hom.: 0 Cov.: 34 AF XY: 0.0000940 AC XY: 7AN XY: 74496
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.589C>T (p.R197C) alteration is located in exon 6 (coding exon 6) of the P2RX5 gene. This alteration results from a C to T substitution at nucleotide position 589, causing the arginine (R) at amino acid position 197 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
0.42, 0.60, 0.53, 0.51
.;B;P;P;.;P
Vest4
MVP
MPC
0.43
ClinPred
T
GERP RS
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gMVP
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