rs1567647066

Variant names:

• chr17-3897863-G-A
• rs1567647066
• NM_002558.4:c.1151C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002558.4(P2RX1):​c.1151C>T​(p.Ala384Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: P2RX1 NM_002558.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0270
• Publications: 0 publications found

Genes affected

P2RX1 (HGNC:8533): (purinergic receptor P2X 1) The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060886204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002558.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX1	NM_002558.4	MANE Select	c.1151C>T	p.Ala384Val	missense	Exon 12 of 12	NP_002549.1	P51575

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX1	ENST00000225538.4	TSL:1 MANE Select	c.1151C>T	p.Ala384Val	missense	Exon 12 of 12	ENSP00000225538.3	P51575
	P2RX1	ENST00000968389.1		c.1211C>T	p.Ala404Val	missense	Exon 12 of 12	ENSP00000638448.1
	P2RX1	ENST00000861554.1		c.1100C>T	p.Ala367Val	missense	Exon 12 of 12	ENSP00000531613.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461636 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727106

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.027
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.066
Sift	Benign	0.57	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.56		Loss of disorder (P = 0.0362)
MVP		0.18
MPC		0.33
ClinPred		0.031	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.037
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1567647066; hg19: chr17-3801157;