rs2075643

Positions:

chr14-50916714-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.1020C>T(p.Asp340=) variant causes a synonymous change. The variant allele was found at a frequency of 0.192 in 1,612,936 control chromosomes in the GnomAD database, including 34,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2974 hom., cov: 33)

Exomes 𝑓: 0.19 ( 31616 hom. )

Consequence

PYGL
NM_002863.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.97

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 14-50916714-G-A is Benign according to our data. Variant chr14-50916714-G-A is described in ClinVar as [Benign]. Clinvar id is 258830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50916714-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 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.1020C>T	p.Asp340=	synonymous_variant	9/20	ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2 linkuse as main transcript	c.918C>T	p.Asp306=	synonymous_variant	8/19		NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8 linkuse as main transcript	c.1020C>T	p.Asp340=	synonymous_variant	9/20	1	NM_002863.5	ENSP00000216392	P1	P06737-1
PYGL	ENST00000532462.5 linkuse as main transcript	c.1020C>T	p.Asp340=	synonymous_variant	9/20	1		ENSP00000431657
PYGL	ENST00000544180.6 linkuse as main transcript	c.918C>T	p.Asp306=	synonymous_variant	8/19	2		ENSP00000443787		P06737-2

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26238

AN:

152098

Hom.:

2968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.239

AC:

60106

AN:

251412

Hom.:

9323

AF XY:

0.230

AC XY:

31266

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0652

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.195

AC:

284209

AN:

1460720

Hom.:

31616

Cov.:

AF XY:

0.194

AC XY:

141273

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.0638

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.424

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.173

AC:

26259

AN:

152216

Hom.:

2974

Cov.:

AF XY:

0.178

AC XY:

13272

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0646

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.185

Hom.:

3714

Bravo

AF:

0.183

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.187

ClinVar

Significance: Benign

Submissions summary: Benign:7

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	Oct 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

9.6

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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