chr17-3688050-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002561.4(P2RX5):​c.943G>T​(p.Ala315Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. A315T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Consequence

P2RX5
NM_002561.4 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53
Variant links:
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]
P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
P2RX5NM_002561.4 linkc.943G>T p.Ala315Ser missense_variant Exon 9 of 12 ENST00000225328.10 NP_002552.2 Q93086-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P2RX5ENST00000225328.10 linkc.943G>T p.Ala315Ser missense_variant Exon 9 of 12 1 NM_002561.4 ENSP00000225328.5 Q93086-3
P2RX5ENST00000697413.1 linkc.943G>T p.Ala315Ser missense_variant Exon 9 of 13 ENSP00000513301.1 A0A8V8TLD3
P2RX5-TAX1BP3ENST00000550383.1 linkn.943G>T non_coding_transcript_exon_variant Exon 9 of 15 2 ENSP00000455681.1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;.;.;T;.;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.82
D;D;D;D;D;D
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Uncertain
2.8
.;.;.;M;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.6
.;D;D;D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.018
.;D;T;D;D;D
Sift4G
Benign
0.10
T;T;T;T;T;T
Polyphen
1.0, 0.99, 0.99, 1.0
.;D;D;D;.;D
Vest4
0.66
MutPred
0.78
.;.;.;Loss of ubiquitination at K314 (P = 0.1516);.;.;
MVP
0.55
MPC
0.53
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.43
gMVP
0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3591344; API