17-3688097-C-G

Variant names:

• chr17-3688097-C-G
• rs750470533
• NM_002561.4:c.896G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002561.4(P2RX5):​c.896G>C​(p.Arg299Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,594,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R299G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: P2RX5 NM_002561.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.579

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]

ACMG classification

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=0.27609017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.896G>C	p.Arg299Thr	missense_variant	Exon 9 of 12	ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.896G>C	p.Arg299Thr	missense_variant	Exon 9 of 12	1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.896G>C	p.Arg299Thr	missense_variant	Exon 9 of 13			ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.896G>C		non_coding_transcript_exon_variant	Exon 9 of 15	2		ENSP00000455681.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151594 Hom.: 0 Cov.: 29

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: 0.000421

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000428 AC: 10 AN: 233518 Hom.: 0 AF XY: 0.0000633 AC XY: 8 AN XY: 126338

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: 0.000354

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000243 AC: 35 AN: 1442810 Hom.: 0 Cov.: 28 AF XY: 0.0000334 AC XY: 24 AN XY: 717722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000380

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151594 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 73990

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ExAC AF: 0.0000413 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.896G>C (p.R299T) alteration is located in exon 9 (coding exon 9) of the P2RX5 gene. This alteration results from a G to C substitution at nucleotide position 896, causing the arginine (R) at amino acid position 299 to be replaced by a threonine (T). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.091	.;.;.;T;.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.79	T;T;T;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;.;L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.6	.;D;D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.010	.;D;T;T;D;D
Sift4G	Benign	0.20	T;T;T;T;T;T
Polyphen		0.85, 0.29, 0.53, 0.73	.;P;B;P;.;P
Vest4		0.59
MutPred		0.68		.;.;.;Loss of MoRF binding (P = 0.0141);.;.;
MVP		0.088
MPC		0.38
ClinPred		0.20	T
GERP RS		-1.9
Varity_R		0.15
gMVP		0.52

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

Other links and lift over

dbSNP: rs750470533; hg19: chr17-3591391;