Variant 17-3690428-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002561.4(P2RX5):c.532G>C(p.Glu178Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

P2RX5
NM_002561.4 missense, splice_region

Scores

Splicing: ADA: 0.0002197

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.264

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 links:

P2RX5-TAX1BP3 (HGNC:):

P2RX5-TAX1BP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.105689645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX5	NM_002561.4 linkuse as main transcript	c.532G>C	p.Glu178Gln	missense_variant, splice_region_variant	5/12	ENST00000225328.10
P2RX5-TAX1BP3	NR_037928.1 linkuse as main transcript	n.931G>C		splice_region_variant, non_coding_transcript_exon_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX5	ENST00000225328.10 linkuse as main transcript	c.532G>C	p.Glu178Gln	missense_variant, splice_region_variant	5/12	1	NM_002561.4		Q93086-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455724

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000992

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Mar 06, 2023

The c.532G>C (p.E178Q) alteration is located in exon 5 (coding exon 5) of the P2RX5 gene. This alteration results from a G to C substitution at nucleotide position 532, causing the glutamic acid (E) at amino acid position 178 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.99

DANN

Benign

0.36

DEOGEN2

Benign

0.013

.;.;.;T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.27

T;T;T;T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

.;.;N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

.;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.50

.;T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;T

Polyphen

0.0040, 0.42

.;B;B;B;.;B

Vest4

0.12

MutPred

0.42

Loss of glycosylation at P177 (P = 0.0654);.;Loss of glycosylation at P177 (P = 0.0654);Loss of glycosylation at P177 (P = 0.0654);.;.;

MVP

0.27

MPC

0.13

ClinPred

0.23

GERP RS

-7.1

Varity_R

0.050

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.016

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over