14-50944311-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002863.5(PYGL):c.93T>C(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 1,612,674 control chromosomes in the GnomAD database, including 2,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 205 hom., cov: 33)

Exomes 𝑓: 0.046 ( 2025 hom. )

Consequence

PYGL
NM_002863.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.10

Publications

6 publications found

Variant links:

Genes affected

PYGL (HGNC:9725): (glycogen phosphorylase L) This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]

PYGL Gene-Disease associations (from GenCC):

glycogen storage disease VI
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet, Ambry Genetics

PYGL links:

ENSG00000294759 (HGNC:):

ENSG00000294759 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-50944311-A-G is Benign according to our data. Variant chr14-50944311-A-G is described in ClinVar as [Benign]. Clinvar id is 258849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5 link	c.93T>C	p.Ser31Ser	synonymous_variant	Exon 1 of 20	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 link	c.93T>C	p.Ser31Ser	synonymous_variant	Exon 1 of 19		NP_001157412.1	P06737-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8 link	c.93T>C	p.Ser31Ser	synonymous_variant	Exon 1 of 20	1	NM_002863.5	ENSP00000216392.7		P06737-1

Frequencies

GnomAD3 genomes

AF:

0.0477

AC:

7194

AN:

150942

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.00881

Gnomad AMR

AF:

0.0883

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0889

Gnomad SAS

AF:

0.0733

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0391

Gnomad OTH

AF:

0.0496

GnomAD2 exomes

AF:

0.0522

AC:

13099

AN:

250882

AF XY:

0.0518

show subpopulations

Gnomad AFR exome

AF:

0.0431

Gnomad AMR exome

AF:

0.0883

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.0864

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0383

Gnomad OTH exome

AF:

0.0492

GnomAD4 exome

AF:

0.0461

AC:

67348

AN:

1461614

Hom.:

2025

Cov.:

AF XY:

0.0465

AC XY:

33840

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.0455

AC:

1521

AN:

33464

American (AMR)

AF:

0.0890

AC:

3978

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0194

AC:

508

AN:

26126

East Asian (EAS)

AF:

0.128

AC:

5076

AN:

39690

South Asian (SAS)

AF:

0.0760

AC:

6558

AN:

86254

European-Finnish (FIN)

AF:

0.0277

AC:

1479

AN:

53364

Middle Eastern (MID)

AF:

0.0392

AC:

226

AN:

5768

European-Non Finnish (NFE)

AF:

0.0405

AC:

45084

AN:

1111864

Other (OTH)

AF:

0.0483

AC:

2918

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

4471

8943

13414

17886

22357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0476

AC:

7197

AN:

151060

Hom.:

205

Cov.:

AF XY:

0.0491

AC XY:

3624

AN XY:

73806

show subpopulations

African (AFR)

AF:

0.0468

AC:

1922

AN:

41072

American (AMR)

AF:

0.0883

AC:

1345

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3460

East Asian (EAS)

AF:

0.0891

AC:

457

AN:

5130

South Asian (SAS)

AF:

0.0732

AC:

349

AN:

4768

European-Finnish (FIN)

AF:

0.0271

AC:

283

AN:

10458

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0391

AC:

2644

AN:

67648

Other (OTH)

AF:

0.0491

AC:

103

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

362

725

1087

1450

1812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0402

Hom.:

105

Bravo

AF:

0.0506

Asia WGS

AF:

0.0800

AC:

277

AN:

3478

EpiCase

AF:

0.0349

EpiControl

AF:

0.0362

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 24, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Glycogen storage disease, type VI

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 13, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

1.1

PromoterAI

0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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14-50944311-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over