Genetic Variant PYGM:c.2313-47T>C (chr11-64747034-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_005609.4(PYGM):c.2313-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,603,890 control chromosomes in the GnomAD database, including 13,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1434 hom., cov: 33)

Exomes 𝑓: 0.11 ( 11589 hom. )

Consequence

PYGM
NM_005609.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.39

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=-1.0).

BP6

Variant 11-64747034-A-G is Benign according to our data. Variant chr11-64747034-A-G is described in ClinVar as [Benign]. Clinvar id is 259834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGM	NM_005609.4 link	c.2313-47T>C		intron_variant	Intron 18 of 19	ENST00000164139.4	NP_005600.1	P11217-1
PYGM	NM_001164716.1 link	c.2049-47T>C		intron_variant	Intron 16 of 17		NP_001158188.1	P11217-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYGM	ENST00000164139.4 link	c.2313-47T>C	intron_variant	Intron 18 of 19	1	NM_005609.4	ENSP00000164139.3	P11217-1
PYGM	ENST00000377432.7 link	c.2049-47T>C	intron_variant	Intron 16 of 17	2		ENSP00000366650.3	P11217-2
PYGM	ENST00000483742.1 link	n.1666-47T>C	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17602

AN:

152054

Hom.:

1431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0903

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.147

AC:

36787

AN:

250096

Hom.:

3994

AF XY:

0.141

AC XY:

19083

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.0782

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.385

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0847

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.106

AC:

154598

AN:

1451718

Hom.:

11589

Cov.:

AF XY:

0.107

AC XY:

77601

AN XY:

722990

show subpopulations

Gnomad4 AFR exome

AF:

0.0760

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0849

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.116

AC:

17630

AN:

152172

Hom.:

1434

Cov.:

AF XY:

0.122

AC XY:

9089

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0798

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0903

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.101

Hom.:

814

Bravo

AF:

0.125

Asia WGS

AF:

0.263

AC:

915

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glycogen storage disease, type V

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

DANN

Benign

0.26

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