chr11-64751590-T-C

Position:

chr11-64751590-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005609.4(PYGM):c.1827+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,936 control chromosomes in the GnomAD database, including 12,555 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1324 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11231 hom. )

Consequence

PYGM
NM_005609.4 splice_region, intron

Scores

Splicing: ADA: 0.0004109

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -0.285

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-64751590-T-C is Benign according to our data. Variant chr11-64751590-T-C is described in ClinVar as [Benign]. Clinvar id is 95294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64751590-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGM	NM_005609.4 link	c.1827+7A>G		splice_region_variant, intron_variant		ENST00000164139.4	NP_005600.1	P11217-1
PYGM	NM_001164716.1 link	c.1563+7A>G		splice_region_variant, intron_variant			NP_001158188.1	P11217-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PYGM	ENST00000164139.4 link	c.1827+7A>G	splice_region_variant, intron_variant	1	NM_005609.4	ENSP00000164139.3	P11217-1
PYGM	ENST00000377432.7 link	c.1563+7A>G	splice_region_variant, intron_variant	2		ENSP00000366650.3	P11217-2
PYGM	ENST00000462303.1 link	n.151+7A>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16966

AN:

152098

Hom.:

1322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0902

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.144

AC:

36293

AN:

251292

Hom.:

3842

AF XY:

0.139

AC XY:

18873

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0845

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.105

AC:

154152

AN:

1461720

Hom.:

11231

Cov.:

AF XY:

0.106

AC XY:

77391

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0668

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0849

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.112

AC:

16993

AN:

152216

Hom.:

1324

Cov.:

AF XY:

0.118

AC XY:

8783

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0696

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.353

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0902

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0934

Hom.:

1068

Bravo

AF:

0.120

Asia WGS

AF:

0.252

AC:

876

AN:

3478

EpiCase

AF:

0.0869

EpiControl

AF:

0.0848

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type V

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jun 03, 2021	- -

not provided

Benign:3Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 28967462) -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 07, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.4

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00041

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.050

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