11-64752454-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005609.4(PYGM):c.1569C>G(p.Leu523Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,210 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 12 hom., cov: 32)

Exomes 𝑓: 0.016 ( 225 hom. )

Consequence

PYGM
NM_005609.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.277

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-64752454-G-C is Benign according to our data. Variant chr11-64752454-G-C is described in ClinVar as [Benign]. Clinvar id is 95293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64752454-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.277 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1784/152366) while in subpopulation NFE AF= 0.0177 (1202/68034). AF 95% confidence interval is 0.0168. There are 12 homozygotes in gnomad4. There are 812 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGM	NM_005609.4 link	c.1569C>G	p.Leu523Leu	synonymous_variant	Exon 13 of 20	ENST00000164139.4	NP_005600.1	P11217-1
PYGM	NM_001164716.1 link	c.1305C>G	p.Leu435Leu	synonymous_variant	Exon 11 of 18		NP_001158188.1	P11217-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGM	ENST00000164139.4 link	c.1569C>G	p.Leu523Leu	synonymous_variant	Exon 13 of 20	1	NM_005609.4	ENSP00000164139.3		P11217-1
PYGM	ENST00000377432.7 link	c.1305C>G	p.Leu435Leu	synonymous_variant	Exon 11 of 18	2		ENSP00000366650.3		P11217-2

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1784

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00477

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0100

AC:

2518

AN:

251342

Hom.:

AF XY:

0.0101

AC XY:

1368

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.00801

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00591

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0163

AC:

23833

AN:

1461844

Hom.:

225

Cov.:

AF XY:

0.0158

AC XY:

11488

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00597

Gnomad4 AMR exome

AF:

0.00841

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00711

Gnomad4 NFE exome

AF:

0.0197

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0117

AC:

1784

AN:

152366

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

812

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00476

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00602

Gnomad4 NFE

AF:

0.0177

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type V

Benign:4

Nov 01, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:3

Apr 11, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 09, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 17, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.4

DANN

Benign

0.61

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

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