rs3216001

Variant names:

• chr14-50905380-CA-C
• rs3216001
• NM_002863.5:c.*11delT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002863.5(PYGL):​c.*11delT 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
• Publications: 8 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: G2P, Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 258828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002863.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGL	NM_002863.5	MANE Select	c.*11delT		3_prime_UTR	Exon 20 of 20	NP_002854.3
	PYGL	NM_001163940.2		c.*11delT		3_prime_UTR	Exon 19 of 19	NP_001157412.1	P06737-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGL	ENST00000216392.8	TSL:1 MANE Select	c.*11delT		3_prime_UTR	Exon 20 of 20	ENSP00000216392.7	P06737-1
	PYGL	ENST00000532462.5	TSL:1	c.2379+2890delT		intron	N/A	ENSP00000431657.1	E9PK47
	PYGL	ENST00000874287.1		c.*11delT		3_prime_UTR	Exon 20 of 20	ENSP00000544346.1

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

GnomAD2 exomes AF: 0.371 AC: 93051 AN: 251102 AF XY: 0.357

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 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

African (AFR) AF: 0.469 AC: 15578 AN: 33182

American (AMR) AF: 0.605 AC: 27039 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6617 AN: 26040

East Asian (EAS) AF: 0.627 AC: 24835 AN: 39606

South Asian (SAS) AF: 0.354 AC: 30407 AN: 85962

European-Finnish (FIN) AF: 0.301 AC: 16071 AN: 53380

Middle Eastern (MID) AF: 0.380 AC: 2178 AN: 5734

European-Non Finnish (NFE) AF: 0.271 AC: 298723 AN: 1101016

Other (OTH) AF: 0.330 AC: 19797 AN: 59964

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

African (AFR) AF: 0.459 AC: 19016 AN: 41454

American (AMR) AF: 0.482 AC: 7353 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 837 AN: 3462

East Asian (EAS) AF: 0.607 AC: 3133 AN: 5158

South Asian (SAS) AF: 0.366 AC: 1760 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3202 AN: 10532

Middle Eastern (MID) AF: 0.428 AC: 124 AN: 290

European-Non Finnish (NFE) AF: 0.273 AC: 18582 AN: 67954

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.309 Hom.: 1394

Bravo AF: 0.384

Asia WGS AF: 0.489 AC: 1699 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Glycogen storage disease, type VI (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3216001; hg19: chr14-51372098; COSMIC: COSV53587647; COSMIC: COSV53587647;