Genetic Variant NM_005446.5:c.155A>G (chr22-21015329-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005446.5(P2RX6):c.155A>G(p.Tyr52Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,551,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

P2RX6
NM_005446.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.32

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: Uncertain_significance. The variant received 0 ACMG points.

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.155A>G	p.Tyr52Cys	missense	Exon 1 of 12	NP_005437.2	O15547-1
P2RX6	NM_001349876.2		c.-223A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001336805.1
P2RX6	NM_001349874.2		c.-291A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001336803.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX6	ENST00000413302.7	TSL:1 MANE Select	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 12	ENSP00000416193.2	O15547-1
P2RX6	ENST00000401443.5	TSL:1	c.86+69A>G		intron	N/A	ENSP00000385309.1	O15547-2
P2RX6	ENST00000422210.5	TSL:1	n.140A>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000407920.1	H7C2V4

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

151574

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD2 exomes

AF:

0.0000450

AC:

AN:

199930

AF XY:

0.0000363

show subpopulations

Gnomad AFR exome

AF:

0.000635

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1399608

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

695548

show subpopulations

African (AFR)

AF:

0.000415

AC:

AN:

28892

American (AMR)

AF:

0.00

AC:

AN:

32910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24076

East Asian (EAS)

AF:

0.00

AC:

AN:

34144

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5292

European-Non Finnish (NFE)

AF:

9.20e-7

AC:

AN:

1087512

Other (OTH)

AF:

0.0000522

AC:

AN:

57482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.000224

AC:

AN:

151574

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

74024

show subpopulations

African (AFR)

AF:

0.000799

AC:

AN:

41278

American (AMR)

AF:

0.0000656

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67926

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000174

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

PhyloP100

5.3

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-7.6

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MVP

0.36

MPC

0.52

ClinPred

0.68

GERP RS

3.3

PromoterAI

-0.025

Neutral

(source)

Varity_R

0.62

gMVP

0.87

Mutation Taster

=97/103

disease causing

(source)

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

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