Variant chr14-50937871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002863.5(PYGL):c.244-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,552,696 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 31 hom., cov: 33)

Exomes 𝑓: 0.019 ( 308 hom. )

Consequence

PYGL
NM_002863.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.148

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-50937871-C-T is Benign according to our data. Variant chr14-50937871-C-T is described in ClinVar as [Benign]. Clinvar id is 258842.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-50937871-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0221 (3358/152268) while in subpopulation AFR AF= 0.0366 (1519/41540). AF 95% confidence interval is 0.035. There are 31 homozygotes in gnomad4. There are 1596 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGL	NM_002863.5 linkuse as main transcript	c.244-34G>A		intron_variant		ENST00000216392.8
PYGL	NM_001163940.2 linkuse as main transcript	c.244-2686G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PYGL	ENST00000216392.8 linkuse as main transcript	c.244-34G>A	intron_variant	1	NM_002863.5	P1	P06737-1
PYGL	ENST00000532462.5 linkuse as main transcript	c.244-34G>A	intron_variant	1
PYGL	ENST00000530336.2 linkuse as main transcript	n.311-34G>A	intron_variant, non_coding_transcript_variant	1
PYGL	ENST00000544180.6 linkuse as main transcript	c.244-2686G>A	intron_variant	2			P06737-2

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3354

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0166

AC:

4123

AN:

248690

Hom.:

AF XY:

0.0164

AC XY:

2211

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.00757

Gnomad EAS exome

AF:

0.0132

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0188

AC:

26380

AN:

1400428

Hom.:

308

Cov.:

AF XY:

0.0188

AC XY:

13172

AN XY:

700268

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.00752

Gnomad4 EAS exome

AF:

0.0247

Gnomad4 SAS exome

AF:

0.0174

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0190

Gnomad4 OTH exome

AF:

0.0214

GnomAD4 genome

AF:

0.0221

AC:

3358

AN:

152268

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1596

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.0173

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00942

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0190

Hom.:

Bravo

AF:

0.0226

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.85

CADD

Benign

0.85

DANN

Benign

0.29

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