rs589691

chr11-64757744-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005609.4(PYGM):c.660+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,613,552 control chromosomes in the GnomAD database, including 597,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (42040 hom., cov: 32)
  • Exomes 𝑓: 0.86 (555601 hom.)
• Consequence: PYGM NM_005609.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.270

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-64757744-C-T is Benign according to our data. Variant chr11-64757744-C-T is described in ClinVar as [Benign]. Clinvar id is 259840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGM	NM_005609.4	c.660+35G>A		intron_variant		ENST00000164139.4
PYGM	NM_001164716.1	c.396+35G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYGM	ENST00000164139.4	c.660+35G>A		intron_variant		1	NM_005609.4	P1
PYGM	ENST00000377432.7	c.396+35G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106032 AN: 152028 Hom.: 42049 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.730

GnomAD3 exomes AF: 0.793 AC: 198705 AN: 250478 Hom.: 82321 AF XY: 0.810 AC XY: 109756 AN XY: 135526

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.851

Gnomad EAS exome AF: 0.616

Gnomad SAS exome AF: 0.810

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.840

GnomAD4 exome AF: 0.864 AC: 1263079 AN: 1461406 Hom.: 555601 Cov.: 53 AF XY: 0.865 AC XY: 628821 AN XY: 726994

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.597

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.888

Gnomad4 NFE exome AF: 0.905

Gnomad4 OTH exome AF: 0.831

GnomAD4 genome AF: 0.697 AC: 106048 AN: 152146 Hom.: 42040 Cov.: 32 AF XY: 0.697 AC XY: 51815 AN XY: 74376

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.728

Alfa AF: 0.862 Hom.: 73060

Bravo AF: 0.665

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Glycogen storage disease, type V Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.30

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

Other links and lift over

dbSNP: rs589691; hg19: chr11-64525216; COSMIC: COSV51217675; COSMIC: COSV51217675;