rs137880110

Positions:

• chr14-50909861-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002863.5(PYGL):​c.2177+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,609,870 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (85 hom.)
• Consequence: PYGL NM_002863.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-50909861-A-G is Benign according to our data. Variant chr14-50909861-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 258837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00219 (333/152328) while in subpopulation EAS AF= 0.039 (202/5178). AF 95% confidence interval is 0.0346. There are 8 homozygotes in gnomad4. There are 209 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGL	NM_002863.5	c.2177+34T>C		intron_variant		ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2	c.2075+34T>C		intron_variant			NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8	c.2177+34T>C		intron_variant		1	NM_002863.5	ENSP00000216392.7
PYGL	ENST00000532462.5	c.2177+34T>C		intron_variant		1		ENSP00000431657.1
PYGL	ENST00000544180.6	c.2075+34T>C		intron_variant		2		ENSP00000443787.1
PYGL	ENST00000532107.2	n.350+34T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152210 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00476 AC: 1196 AN: 251322 Hom.: 25 AF XY: 0.00498 AC XY: 677 AN XY: 135840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0393

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.00527

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00239 AC: 3486 AN: 1457542 Hom.: 85 Cov.: 31 AF XY: 0.00266 AC XY: 1928 AN XY: 725432

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0497

Gnomad4 SAS exome AF: 0.0112

Gnomad4 FIN exome AF: 0.00491

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00219 AC: 333 AN: 152328 Hom.: 8 Cov.: 32 AF XY: 0.00281 AC XY: 209 AN XY: 74480

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.57
DANN	Benign	0.28

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: rs137880110; hg19: chr14-51376579;