rs11356035

Positions:

• chr14-50911872-CTT-C
• chr14-50911872-CTT-CT
• chr14-50911872-CTT-CTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate

The ENST00000216392.8(PYGL):​c.1828-3_1828-2del variant causes a splice acceptor, splice polypyrimidine tract, intron change. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PYGL ENST00000216392.8 splice_acceptor, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48

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 Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.05542453 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.3, offset of 0 (no position change), new splice context is: cgtttgaccttcttccccAGgct. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGL	NM_002863.5	c.1828-3_1828-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2	c.1726-3_1726-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8	c.1828-3_1828-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002863.5	ENSP00000216392	P1
PYGL	ENST00000532462.5	c.1828-3_1828-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000431657
PYGL	ENST00000544180.6	c.1726-3_1726-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000443787
PYGL	ENST00000532107.2			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

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: rs11356035; hg19: chr14-51378590;