Variant rs61884454 details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00500

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=-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/exons	MANE	Protein	UniProt
PYGM	NM_005609.4 linkuse as main transcript	c.425-22C>T		intron_variant		ENST00000164139.4	NP_005600.1
PYGM	NM_001164716.1 linkuse as main transcript	c.244-105C>T		intron_variant			NP_001158188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGM	ENST00000164139.4 linkuse as main transcript	c.425-22C>T		intron_variant		1	NM_005609.4	ENSP00000164139	P1	P11217-1
PYGM	ENST00000377432.7 linkuse as main transcript	c.244-105C>T		intron_variant		2		ENSP00000366650		P11217-2

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3793

AN:

152064

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0304

AC XY:

22073

AN XY:

726598

show subpopulations

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.:

Cov.:

AF XY:

0.0247

AC XY:

1835

AN XY:

74406

show subpopulations

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.:

Bravo

AF:

0.0296

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

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

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