chr14-50920940-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.772+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 1,593,836 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 74 hom., cov: 32)

Exomes 𝑓: 0.027 ( 825 hom. )

Consequence

PYGL
NM_002863.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0200

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-50920940-C-A is Benign according to our data. Variant chr14-50920940-C-A is described in ClinVar as Benign. ClinVar VariationId is 258847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5 link	c.772+16G>T		intron_variant	Intron 6 of 19	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 link	c.670+16G>T		intron_variant	Intron 5 of 18		NP_001157412.1	P06737-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYGL	ENST00000216392.8 link	c.772+16G>T	intron_variant	Intron 6 of 19	1	NM_002863.5	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5 link	c.772+16G>T	intron_variant	Intron 6 of 19	1		ENSP00000431657.1	E9PK47
PYGL	ENST00000544180.6 link	c.670+16G>T	intron_variant	Intron 5 of 18	2		ENSP00000443787.1	P06737-2
PYGL	ENST00000553872.1 link	n.573+16G>T	intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3523

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00676

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0902

Gnomad SAS

AF:

0.0516

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0316

AC:

7930

AN:

251322

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.0325

Gnomad ASJ exome

AF:

0.00963

Gnomad EAS exome

AF:

0.0985

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.0225

Gnomad OTH exome

AF:

0.0249

GnomAD4 exome

AF:

0.0269

AC:

38825

AN:

1441538

Hom.:

825

Cov.:

AF XY:

0.0276

AC XY:

19792

AN XY:

718364

show subpopulations

African (AFR)

AF:

0.00776

AC:

256

AN:

32992

American (AMR)

AF:

0.0344

AC:

1536

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

293

AN:

25988

East Asian (EAS)

AF:

0.112

AC:

4443

AN:

39618

South Asian (SAS)

AF:

0.0514

AC:

4412

AN:

85802

European-Finnish (FIN)

AF:

0.0207

AC:

1106

AN:

53400

Middle Eastern (MID)

AF:

0.0235

AC:

134

AN:

5706

European-Non Finnish (NFE)

AF:

0.0229

AC:

25011

AN:

1093626

Other (OTH)

AF:

0.0274

AC:

1634

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1726

3452

5179

6905

8631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1040

2080

3120

4160

5200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3527

AN:

152298

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

1846

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00693

AC:

288

AN:

41554

American (AMR)

AF:

0.0483

AC:

739

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.0900

AC:

467

AN:

5188

South Asian (SAS)

AF:

0.0512

AC:

247

AN:

4826

European-Finnish (FIN)

AF:

0.0203

AC:

216

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0216

AC:

1470

AN:

68034

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

165

330

496

661

826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0198

Hom.:

Bravo

AF:

0.0234

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 26, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease, type VI

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.77

CADD

Benign

1.7

(source)

DANN

Benign

0.64

PhyloP100

0.020

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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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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