rs34096980

Variant names:

• chr14-50924018-T-A
• rs34096980
• NM_002863.5:c.611A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-50924018-T-A
• chr14-50924018-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002863.5(PYGL):​c.611A>T​(p.Tyr204Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y204C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PYGL NM_002863.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• glycogen storage disease VI

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5	c.611A>T	p.Tyr204Phe	missense_variant	Exon 5 of 20	ENST00000216392.8	NP_002854.3
PYGL	NM_001163940.2	c.509A>T	p.Tyr170Phe	missense_variant	Exon 4 of 19		NP_001157412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGL	ENST00000216392.8	c.611A>T	p.Tyr204Phe	missense_variant	Exon 5 of 20	1	NM_002863.5	ENSP00000216392.7
PYGL	ENST00000532462.5	c.611A>T	p.Tyr204Phe	missense_variant	Exon 5 of 20	1		ENSP00000431657.1
PYGL	ENST00000530336.2	n.678A>T		non_coding_transcript_exon_variant	Exon 5 of 5	1
PYGL	ENST00000544180.6	c.509A>T	p.Tyr170Phe	missense_variant	Exon 4 of 19	2		ENSP00000443787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.56	.;.;D
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.7	.;.;L
PhyloP100		6.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.56
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.038	B;.;B
Vest4		0.66
MutPred		0.64		Gain of methylation at K206 (P = 0.0443);.;Gain of methylation at K206 (P = 0.0443);
MVP		0.93
MPC		0.52
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.61
gMVP		0.71
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34096980; hg19: chr14-51390736;