Variant chr11-64759747-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_005609.4(PYGM):c.152A>G(p.Asp51Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PYGM
NM_005609.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:3

Conservation

PhyloP100: 7.80

Variant links:

Genes affected

PYGM (HGNC:9726): (glycogen phosphorylase, muscle associated) This gene encodes a muscle enzyme involved in glycogenolysis. Highly similar enzymes encoded by different genes are found in liver and brain. Mutations in this gene are associated with McArdle disease (myophosphorylase deficiency), a glycogen storage disease of muscle. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

PYGM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.896

PP5

Variant 11-64759747-T-C is Pathogenic according to our data. Variant chr11-64759747-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 40042.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64759747-T-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGM	NM_005609.4 linkuse as main transcript	c.152A>G	p.Asp51Gly	missense_variant	1/20	ENST00000164139.4	NP_005600.1	P11217-1
PYGM	NM_001164716.1 linkuse as main transcript	c.152A>G	p.Asp51Gly	missense_variant	1/18		NP_001158188.1	P11217-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGM	ENST00000164139.4 linkuse as main transcript	c.152A>G	p.Asp51Gly	missense_variant	1/20	1	NM_005609.4	ENSP00000164139.3		P11217-1
PYGM	ENST00000377432.7 linkuse as main transcript	c.152A>G	p.Asp51Gly	missense_variant	1/18	2		ENSP00000366650.3		P11217-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type V

Pathogenic:3

Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 01, 2011	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Mar 18, 2020	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 10, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Pathogenic

0.86

Sift

Benign

0.19

T;D

Sift4G

Uncertain

0.045

D;D

Polyphen

0.99

.;D

Vest4

0.94

MutPred

0.50

Loss of stability (P = 0.0407);Loss of stability (P = 0.0407);

MVP

0.99

MPC

0.97

ClinPred

1.0

GERP RS

5.6

Varity_R

0.94

gMVP

0.83

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over