rs3216001

Positions:

• chr14-50905380-CA-C
• chr14-50905380-CA-CAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002863.5(PYGL):​c.*11del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10889 hom., cov: 0)
  • Exomes 𝑓: 0.30 (73702 hom.)
• Consequence: PYGL NM_002863.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 14-50905380-CA-C is Benign according to our data. Variant chr14-50905380-CA-C is described in ClinVar as [Benign]. Clinvar id is 258828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50905380-CA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGL	NM_002863.5	c.*11del		3_prime_UTR_variant	20/20	ENST00000216392.8
PYGL	NM_001163940.2	c.*11del		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYGL	ENST00000216392.8	c.*11del		3_prime_UTR_variant	20/20	1	NM_002863.5	P1
PYGL	ENST00000532462.5	c.2379+2890del		intron_variant		1
PYGL	ENST00000544180.6	c.*11del		3_prime_UTR_variant	19/19	2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54825 AN: 151826 Hom.: 10854 Cov.: 0

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.371 AC: 93051 AN: 251102 Hom.: 19890 AF XY: 0.357 AC XY: 48385 AN XY: 135692

Gnomad AFR exome AF: 0.457

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.603

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.304 AC: 441245 AN: 1449560 Hom.: 73702 Cov.: 0 AF XY: 0.304 AC XY: 219596 AN XY: 721956

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.605

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.361 AC: 54906 AN: 151944 Hom.: 10889 Cov.: 0 AF XY: 0.367 AC XY: 27278 AN XY: 74258

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.376

Alfa AF: 0.309 Hom.: 1394

Bravo AF: 0.384

Asia WGS AF: 0.489 AC: 1699 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Glycogen storage disease, type VI Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3216001; hg19: chr14-51372098;