rs200740801

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005446.5(P2RX6):c.392C>T(p.Pro131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,555,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

P2RX6
NM_005446.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Publications

3 publications found

Variant links:

Genes affected

P2RX6 (HGNC:8538): (purinergic receptor P2X 6) The protein encoded by this gene belongs to the family of P2X receptors, which are ATP-gated ion channels and mediate rapid and selective permeability to cations. This gene is predominantly expressed in skeletal muscle, and regulated by p53. The encoded protein is associated with VE-cadherin at the adherens junctions of human umbilical vein endothelial cells. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 22, has been identified. [provided by RefSeq, Apr 2009]

P2RX6 Gene-Disease associations (from GenCC):

myopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

P2RX6 links:

ENSG00000291240 (HGNC:):

ENSG00000291240 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41511652).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005446.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX6	NM_005446.5	MANE Select	c.392C>T	p.Pro131Leu	missense	Exon 4 of 12	NP_005437.2	O15547-1
P2RX6	NM_001394691.1		c.392C>T	p.Pro131Leu	missense	Exon 4 of 12	NP_001381620.1
P2RX6	NM_001394692.1		c.392C>T	p.Pro131Leu	missense	Exon 4 of 11	NP_001381621.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX6	ENST00000413302.7	TSL:1 MANE Select	c.392C>T	p.Pro131Leu	missense	Exon 4 of 12	ENSP00000416193.2	O15547-1
P2RX6	ENST00000401443.5	TSL:1	c.314C>T	p.Pro105Leu	missense	Exon 4 of 12	ENSP00000385309.1	O15547-2
P2RX6	ENST00000432930.5	TSL:1	n.375C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000404223.1	H7C266

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000465

AC:

AN:

193728

AF XY:

0.0000387

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000341

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1403218

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

692906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31732

American (AMR)

AF:

0.00

AC:

AN:

36394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22356

East Asian (EAS)

AF:

0.000103

AC:

AN:

38886

South Asian (SAS)

AF:

0.00

AC:

AN:

75724

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.0000129

AC:

AN:

1083952

Other (OTH)

AF:

0.0000173

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000702

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000579

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

M_CAP

Benign

0.073

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

PhyloP100

1.8

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.53

MutPred

0.59

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.28

MPC

0.47

ClinPred

0.92

GERP RS

4.5

Varity_R

0.32

gMVP

0.39

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over