Genetic Variant NM_005446.5:c.718G>A (chr22-21023354-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005446.5(P2RX6):c.718G>A(p.Val240Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,910 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: 0.000021 ( 0 hom. )

Consequence

P2RX6
NM_005446.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

0 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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.302095).

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.718G>A	p.Val240Met	missense	Exon 7 of 12	NP_005437.2	O15547-1
P2RX6	NM_001394691.1		c.718G>A	p.Val240Met	missense	Exon 7 of 12	NP_001381620.1
P2RX6	NM_001394692.1		c.718G>A	p.Val240Met	missense	Exon 7 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.718G>A	p.Val240Met	missense	Exon 7 of 12	ENSP00000416193.2	O15547-1
P2RX6	ENST00000401443.5	TSL:1	c.640G>A	p.Val214Met	missense	Exon 7 of 12	ENSP00000385309.1	O15547-2
P2RX6	ENST00000422210.5	TSL:1	n.*249G>A		non_coding_transcript_exon	Exon 5 of 11	ENSP00000407920.1	H7C2V4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251152

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111864

Other (OTH)

AF:

0.0000663

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41538

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000659

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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

Uncertain

0.40

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

0.070

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.018

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

2.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.3

REVEL

Benign

0.16

Sift

Uncertain

0.025

Sift4G

Uncertain

0.051

Polyphen

0.98

Vest4

0.45

MVP

0.13

MPC

0.41

ClinPred

0.27

GERP RS

2.2

Varity_R

0.079

gMVP

0.36

Mutation Taster

=95/5

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