rs61731001

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002558.4(P2RX1):​c.1142G>T​(p.Arg381Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

P2RX1
NM_002558.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.89
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053330243).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
P2RX1NM_002558.4 linkc.1142G>T p.Arg381Leu missense_variant Exon 12 of 12 ENST00000225538.4 NP_002549.1 P51575

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P2RX1ENST00000225538.4 linkc.1142G>T p.Arg381Leu missense_variant Exon 12 of 12 1 NM_002558.4 ENSP00000225538.3 P51575
P2RX1ENST00000572418.1 linkn.1665G>T non_coding_transcript_exon_variant Exon 11 of 11 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152050
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250644
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135564
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461716
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152050
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.013
DANN
Benign
0.85
DEOGEN2
Benign
0.26
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.44
N
REVEL
Benign
0.010
Sift
Benign
0.52
T
Sift4G
Benign
0.34
T
Polyphen
0.058
B
Vest4
0.14
MutPred
0.48
Loss of solvent accessibility (P = 0.0052);
MVP
0.10
MPC
0.47
ClinPred
0.049
T
GERP RS
-5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.042
gMVP
0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61731001; hg19: chr17-3801166; API