Variant 14-50905597-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.2380-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,595,938 control chromosomes in the GnomAD database, including 695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 91 hom., cov: 33)

Exomes 𝑓: 0.024 ( 604 hom. )

Consequence

PYGL
NM_002863.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.137

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-50905597-C-T is Benign according to our data. Variant chr14-50905597-C-T is described in ClinVar as [Benign]. Clinvar id is 258839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGL	NM_002863.5 linkuse as main transcript	c.2380-41G>A		intron_variant		ENST00000216392.8
PYGL	NM_001163940.2 linkuse as main transcript	c.2278-41G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PYGL	ENST00000216392.8 linkuse as main transcript	c.2380-41G>A	intron_variant	1	NM_002863.5	P1	P06737-1
PYGL	ENST00000532462.5 linkuse as main transcript	c.2379+2674G>A	intron_variant	1
PYGL	ENST00000544180.6 linkuse as main transcript	c.2278-41G>A	intron_variant	2			P06737-2

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4677

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0498

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0309

AC:

7749

AN:

250550

Hom.:

172

AF XY:

0.0296

AC XY:

4008

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.0620

Gnomad SAS exome

AF:

0.0337

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0237

AC:

34159

AN:

1443690

Hom.:

604

Cov.:

AF XY:

0.0237

AC XY:

17063

AN XY:

719568

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.0584

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.0774

Gnomad4 SAS exome

AF:

0.0338

Gnomad4 FIN exome

AF:

0.0247

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0308

AC:

4686

AN:

152248

Hom.:

Cov.:

AF XY:

0.0321

AC XY:

2393

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0443

Gnomad4 AMR

AF:

0.0497

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.0641

Gnomad4 SAS

AF:

0.0332

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0334

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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