rs569602

Variant names:

• chr11-64747034-A-G
• rs569602
• NM_005609.4:c.2313-47T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-64747034-A-G
• chr11-64747034-A-C
• chr11-64747034-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.39
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• glycogen storage disease V

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGM	NM_005609.4	MANE Select	c.2313-47T>C		intron	N/A	NP_005600.1	P11217-1
	PYGM	NM_001164716.1		c.2049-47T>C		intron	N/A	NP_001158188.1	P11217-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGM	ENST00000164139.4	TSL:1 MANE Select	c.2313-47T>C		intron	N/A	ENSP00000164139.3	P11217-1
	PYGM	ENST00000967737.1		c.2412-47T>C		intron	N/A	ENSP00000637796.1
	PYGM	ENST00000938870.1		c.2229-47T>C		intron	N/A	ENSP00000608929.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17602 AN: 152054 Hom.: 1431 Cov.: 33

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

GnomAD2 exomes AF: 0.147 AC: 36787 AN: 250096 AF XY: 0.141

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 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.: 30 AF XY: 0.107 AC XY: 77601 AN XY: 722990

African (AFR) AF: 0.0760 AC: 2524 AN: 33222

American (AMR) AF: 0.291 AC: 12989 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3247 AN: 26072

East Asian (EAS) AF: 0.403 AC: 15977 AN: 39648

South Asian (SAS) AF: 0.153 AC: 13175 AN: 85992

European-Finnish (FIN) AF: 0.110 AC: 5887 AN: 53398

Middle Eastern (MID) AF: 0.0752 AC: 432 AN: 5744

European-Non Finnish (NFE) AF: 0.0849 AC: 93620 AN: 1103000

Other (OTH) AF: 0.112 AC: 6747 AN: 60040

GnomAD4 genome AF: 0.116 AC: 17630 AN: 152172 Hom.: 1434 Cov.: 33 AF XY: 0.122 AC XY: 9089 AN XY: 74398

African (AFR) AF: 0.0798 AC: 3314 AN: 41518

American (AMR) AF: 0.229 AC: 3500 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1989 AN: 5170

South Asian (SAS) AF: 0.163 AC: 785 AN: 4818

European-Finnish (FIN) AF: 0.110 AC: 1161 AN: 10588

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0903 AC: 6141 AN: 68006

Other (OTH) AF: 0.117 AC: 248 AN: 2116

Alfa AF: 0.101 Hom.: 949

Bravo AF: 0.125

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disease, type V (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.26
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs569602; hg19: chr11-64514506; COSMIC: COSV51218014; COSMIC: COSV51218014;