rs61884454

Variant names:

• chr11-64758371-G-A
• rs61884454
• NM_005609.4:c.425-22C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64758371-G-A
• chr11-64758371-G-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.425-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,612,576 control chromosomes in the GnomAD database, including 1,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (75 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1089 hom.)
• Consequence: PYGM NM_005609.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00500

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=-0.8).
• BP6: Variant 11-64758371-G-A is Benign according to our data. Variant chr11-64758371-G-A is described in ClinVar as [Benign]. Clinvar id is 259836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64758371-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGM	NM_005609.4	c.425-22C>T		intron_variant	Intron 3 of 19	ENST00000164139.4	NP_005600.1
PYGM	NM_001164716.1	c.244-105C>T		intron_variant	Intron 1 of 17		NP_001158188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGM	ENST00000164139.4	c.425-22C>T		intron_variant	Intron 3 of 19	1	NM_005609.4	ENSP00000164139.3
PYGM	ENST00000377432.7	c.244-105C>T		intron_variant	Intron 1 of 17	2		ENSP00000366650.3

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3793 AN: 152064 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00814

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0370 AC: 9269 AN: 250742 Hom.: 423 AF XY: 0.0330 AC XY: 4475 AN XY: 135598

Gnomad AFR exome AF: 0.00764

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.000490

Gnomad SAS exome AF: 0.0147

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0299

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0312 AC: 45513 AN: 1460394 Hom.: 1089 Cov.: 34 AF XY: 0.0304 AC XY: 22073 AN XY: 726598

Gnomad4 AFR exome AF: 0.00511

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.00662

Gnomad4 EAS exome AF: 0.00139

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0320

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.0250 AC: 3803 AN: 152182 Hom.: 75 Cov.: 32 AF XY: 0.0247 AC XY: 1835 AN XY: 74406

Gnomad4 AFR AF: 0.00811

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0156 Hom.: 8

Bravo AF: 0.0296

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2016

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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs61884454; hg19: chr11-64525843;