Variant 11-64753470-G-T 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.1403+49C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,533,780 control chromosomes in the GnomAD database, including 574,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 44155 hom., cov: 30)

Exomes 𝑓: 0.87 ( 530055 hom. )

Consequence

PYGM
NM_005609.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.737

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=-0.87).

BP6

Variant 11-64753470-G-T is Benign according to our data. Variant chr11-64753470-G-T is described in ClinVar as [Benign]. Clinvar id is 259830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.893 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.1403+49C>A		intron_variant		ENST00000164139.4	NP_005600.1	P11217-1
PYGM	NM_001164716.1 linkuse as main transcript	c.1139+49C>A		intron_variant			NP_001158188.1	P11217-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGM	ENST00000164139.4 linkuse as main transcript	c.1403+49C>A		intron_variant		1	NM_005609.4	ENSP00000164139.3		P11217-1
PYGM	ENST00000377432.7 linkuse as main transcript	c.1139+49C>A		intron_variant		2		ENSP00000366650.3		P11217-2

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111529

AN:

151642

Hom.:

44161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.967

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.791

AC:

116721

AN:

147636

Hom.:

47663

AF XY:

0.804

AC XY:

64357

AN XY:

80092

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.679

Gnomad ASJ exome

AF:

0.855

Gnomad EAS exome

AF:

0.618

Gnomad SAS exome

AF:

0.808

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.903

Gnomad OTH exome

AF:

0.842

GnomAD4 exome

AF:

0.870

AC:

1202719

AN:

1382020

Hom.:

530055

Cov.:

AF XY:

0.870

AC XY:

592518

AN XY:

681078

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.853

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.802

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.906

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.735

AC:

111555

AN:

151760

Hom.:

44155

Cov.:

AF XY:

0.734

AC XY:

54401

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.850

Gnomad4 EAS

AF:

0.617

Gnomad4 SAS

AF:

0.792

Gnomad4 FIN

AF:

0.889

Gnomad4 NFE

AF:

0.898

Gnomad4 OTH

AF:

0.762

Alfa

AF:

0.819

Hom.:

10765

Bravo

AF:

0.707

Asia WGS

AF:

0.688

AC:

2391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.8

DANN

Benign

0.85

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

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