14-50944311-A-G

Position:

chr14-50944311-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 links:

PYGL (HGNC:):

PYGL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PYGL	NM_002863.5 linkuse as main transcript	c.93T>C	p.Ser31Ser	synonymous_variant	1/20	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 linkuse as main transcript	c.93T>C	p.Ser31Ser	synonymous_variant	1/19		NP_001157412.1	P06737-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PYGL	ENST00000216392.8 linkuse as main transcript	c.93T>C	p.Ser31Ser	synonymous_variant	1/20	1	NM_002863.5	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5 linkuse as main transcript	c.93T>C	p.Ser31Ser	synonymous_variant	1/20	1		ENSP00000431657.1	E9PK47
PYGL	ENST00000530336.2 linkuse as main transcript	n.160T>C		non_coding_transcript_exon_variant	1/5	1
PYGL	ENST00000544180.6 linkuse as main transcript	c.93T>C	p.Ser31Ser	synonymous_variant	1/19	2		ENSP00000443787.1	P06737-2

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

GnomAD3 exomes

AF:

0.0522

AC:

13099

AN:

250882

Hom.:

456

AF XY:

0.0518

AC XY:

7036

AN XY:

135786

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 SAS exome

AF:

0.0779

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

Gnomad4 AFR exome

AF:

0.0455

Gnomad4 AMR exome

AF:

0.0890

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.0760

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0405

Gnomad4 OTH exome

AF:

0.0483

GnomAD4 genome

AF:

0.0476

AC:

7197

AN:

151060

Hom.:

205

Cov.:

AF XY:

0.0491

AC XY:

3624

AN XY:

73806

show subpopulations

Gnomad4 AFR

AF:

0.0468

Gnomad4 AMR

AF:

0.0883

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.0891

Gnomad4 SAS

AF:

0.0732

Gnomad4 FIN

AF:

0.0271

Gnomad4 NFE

AF:

0.0391

Gnomad4 OTH

AF:

0.0491

Alfa

AF:

0.0401

Hom.:

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

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Apr 24, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Glycogen storage disease, type VI

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 13, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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