dbSNP rs140390791: P2RX6:p.Ala60Thr (chr22-21015955-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005446.5(P2RX6):c.178G>A(p.Ala60Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,549,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A60S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

P2RX6
NM_005446.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064775646).

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.178G>A	p.Ala60Thr	missense	Exon 2 of 12	NP_005437.2	O15547-1
P2RX6	NM_001394691.1		c.178G>A	p.Ala60Thr	missense	Exon 2 of 12	NP_001381620.1
P2RX6	NM_001394692.1		c.178G>A	p.Ala60Thr	missense	Exon 2 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.178G>A	p.Ala60Thr	missense	Exon 2 of 12	ENSP00000416193.2	O15547-1
P2RX6	ENST00000401443.5	TSL:1	c.100G>A	p.Ala34Thr	missense	Exon 2 of 12	ENSP00000385309.1	O15547-2
P2RX6	ENST00000422210.5	TSL:1	n.163G>A		non_coding_transcript_exon	Exon 2 of 11	ENSP00000407920.1	H7C2V4

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000478

GnomAD2 exomes

AF:

0.000286

AC:

AN:

157310

AF XY:

0.000230

show subpopulations

Gnomad AFR exome

AF:

0.00420

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000629

Gnomad NFE exome

AF:

0.0000329

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000162

AC:

227

AN:

1397438

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

105

AN XY:

689240

show subpopulations

African (AFR)

AF:

0.00511

AC:

161

AN:

31534

American (AMR)

AF:

0.000224

AC:

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25164

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35736

South Asian (SAS)

AF:

0.0000884

AC:

AN:

79150

European-Finnish (FIN)

AF:

0.000122

AC:

AN:

49318

Middle Eastern (MID)

AF:

0.000733

AC:

AN:

4090

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1078920

Other (OTH)

AF:

0.000519

AC:

AN:

57848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.00109

AC:

166

AN:

152202

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00388

AC:

161

AN:

41522

American (AMR)

AF:

0.000262

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000383

Hom.:

Bravo

AF:

0.00109

ESP6500AA

AF:

0.00357

AC:

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.000237

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.8

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.28

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.36

PhyloP100

-1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.14

REVEL

Benign

0.030

Sift

Benign

0.42

Sift4G

Benign

0.40

Polyphen

0.0040

Vest4

0.11

MVP

0.11

MPC

0.084

ClinPred

0.0040

GERP RS

-5.0

Varity_R

0.021

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(source)

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

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