chr14-50909960-A-G

Position:

chr14-50909960-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.2112T>C(p.Ala704Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,614,156 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 161 hom. )

Consequence

PYGL
NM_002863.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.37

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=-0.52).

BP6

Variant 14-50909960-A-G is Benign according to our data. Variant chr14-50909960-A-G is described in ClinVar as [Benign]. Clinvar id is 194735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0532 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.2112T>C	p.Ala704Ala	synonymous_variant	17/20	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 linkuse as main transcript	c.2010T>C	p.Ala670Ala	synonymous_variant	16/19		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.2112T>C	p.Ala704Ala	synonymous_variant	17/20	1	NM_002863.5	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5 linkuse as main transcript	c.2112T>C	p.Ala704Ala	synonymous_variant	17/20	1		ENSP00000431657.1	E9PK47
PYGL	ENST00000544180.6 linkuse as main transcript	c.2010T>C	p.Ala670Ala	synonymous_variant	16/19	2		ENSP00000443787.1	P06737-2
PYGL	ENST00000532107.2 linkuse as main transcript	n.285T>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.0122

AC:

3063

AN:

251470

Hom.:

AF XY:

0.0109

AC XY:

1476

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0480

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0427

Gnomad SAS exome

AF:

0.00986

Gnomad FIN exome

AF:

0.00905

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.00426

AC:

6225

AN:

1461890

Hom.:

161

Cov.:

AF XY:

0.00426

AC XY:

3095

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.0477

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0552

Gnomad4 SAS exome

AF:

0.00995

Gnomad4 FIN exome

AF:

0.00912

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00442

GnomAD4 genome

AF:

0.00616

AC:

938

AN:

152266

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

573

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0432

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00811

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00825

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type VI

Benign:3

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 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 23, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 26, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.32

DANN

Benign

0.84

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