Variant rs589691 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.660+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,613,552 control chromosomes in the GnomAD database, including 597,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 42040 hom., cov: 32)

Exomes 𝑓: 0.86 ( 555601 hom. )

Consequence

PYGM
NM_005609.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.270

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=-0.83).

BP6

Variant 11-64757744-C-T is Benign according to our data. Variant chr11-64757744-C-T is described in ClinVar as [Benign]. Clinvar id is 259840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGM	NM_005609.4 linkuse as main transcript	c.660+35G>A		intron_variant		ENST00000164139.4
PYGM	NM_001164716.1 linkuse as main transcript	c.396+35G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYGM	ENST00000164139.4 linkuse as main transcript	c.660+35G>A		intron_variant		1	NM_005609.4	P1	P11217-1
PYGM	ENST00000377432.7 linkuse as main transcript	c.396+35G>A		intron_variant		2			P11217-2

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

106032

AN:

152028

Hom.:

42049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.967

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.730

GnomAD3 exomes

AF:

0.793

AC:

198705

AN:

250478

Hom.:

82321

AF XY:

0.810

AC XY:

109756

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.851

Gnomad EAS exome

AF:

0.616

Gnomad SAS exome

AF:

0.810

Gnomad FIN exome

AF:

0.885

Gnomad NFE exome

AF:

0.902

Gnomad OTH exome

AF:

0.840

GnomAD4 exome

AF:

0.864

AC:

1263079

AN:

1461406

Hom.:

555601

Cov.:

AF XY:

0.865

AC XY:

628821

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.288

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.848

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.804

Gnomad4 FIN exome

AF:

0.888

Gnomad4 NFE exome

AF:

0.905

Gnomad4 OTH exome

AF:

0.831

GnomAD4 genome

AF:

0.697

AC:

106048

AN:

152146

Hom.:

42040

Cov.:

AF XY:

0.697

AC XY:

51815

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.683

Gnomad4 ASJ

AF:

0.846

Gnomad4 EAS

AF:

0.617

Gnomad4 SAS

AF:

0.792

Gnomad4 FIN

AF:

0.889

Gnomad4 NFE

AF:

0.898

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.862

Hom.:

73060

Bravo

AF:

0.665

Asia WGS

AF:

0.680

AC:

2365

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

-0.83

CADD

Benign

1.0

DANN

Benign

0.30

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