rs11231865

Variant names:

• chr11-64753097-G-A
• rs11231865
• NM_005609.4:c.1494C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005609.4(PYGM):​c.1494C>T​(p.Pro498Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,613,600 control chromosomes in the GnomAD database, including 527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (282 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (245 hom.)
• Consequence: PYGM NM_005609.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: -4.89
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-64753097-G-A is Benign according to our data. Variant chr11-64753097-G-A is described in ClinVar as Benign. ClinVar VariationId is 95292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 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.1494C>T	p.Pro498Pro	synonymous	Exon 12 of 20	NP_005600.1	P11217-1
	PYGM	NM_001164716.1		c.1230C>T	p.Pro410Pro	synonymous	Exon 10 of 18	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.1494C>T	p.Pro498Pro	synonymous	Exon 12 of 20	ENSP00000164139.3	P11217-1
	PYGM	ENST00000967737.1		c.1593C>T	p.Pro531Pro	synonymous	Exon 13 of 21	ENSP00000637796.1
	PYGM	ENST00000938870.1		c.1410C>T	p.Pro470Pro	synonymous	Exon 12 of 20	ENSP00000608929.1

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5047 AN: 152144 Hom.: 280 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00862 AC: 2167 AN: 251466 AF XY: 0.00618

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00561

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00327 AC: 4774 AN: 1461338 Hom.: 245 Cov.: 32 AF XY: 0.00275 AC XY: 2002 AN XY: 727002

African (AFR) AF: 0.113 AC: 3794 AN: 33458

American (AMR) AF: 0.00640 AC: 286 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00333 AC: 87 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5766

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1111546

Other (OTH) AF: 0.00656 AC: 396 AN: 60376

GnomAD4 genome AF: 0.0332 AC: 5053 AN: 152262 Hom.: 282 Cov.: 33 AF XY: 0.0313 AC XY: 2327 AN XY: 74450

African (AFR) AF: 0.115 AC: 4797 AN: 41534

American (AMR) AF: 0.0116 AC: 178 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68022

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0130 Hom.: 152

Bravo AF: 0.0371

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Glycogen storage disease, type V (4)
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		-4.9
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11231865; hg19: chr11-64520569; COSMIC: COSV51217162; COSMIC: COSV51217162;