rs17123173

Variant names:

• chr14-50920940-C-A
• rs17123173
• NM_002863.5:c.772+16G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-50920940-C-A
• chr14-50920940-C-G
• chr14-50920940-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002863.5(PYGL):​c.772+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 1,593,836 control chromosomes in the GnomAD database, including 899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (74 hom., cov: 32)
  • Exomes 𝑓: 0.027 (825 hom.)
• Consequence: PYGL NM_002863.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0200
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-50920940-C-A is Benign according to our data. Variant chr14-50920940-C-A is described in ClinVar as Benign. ClinVar VariationId is 258847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0833 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.772+16G>T		intron	N/A	NP_002854.3
	PYGL	NM_001163940.2		c.670+16G>T		intron	N/A	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.772+16G>T		intron	N/A	ENSP00000216392.7	P06737-1
	PYGL	ENST00000532462.5	TSL:1	c.772+16G>T		intron	N/A	ENSP00000431657.1	E9PK47
	PYGL	ENST00000874287.1		c.787+16G>T		intron	N/A	ENSP00000544346.1

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3523 AN: 152180 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.00676

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.0316 AC: 7930 AN: 251322 AF XY: 0.0324

Gnomad AFR exome AF: 0.00769

Gnomad AMR exome AF: 0.0325

Gnomad ASJ exome AF: 0.00963

Gnomad EAS exome AF: 0.0985

Gnomad FIN exome AF: 0.0199

Gnomad NFE exome AF: 0.0225

Gnomad OTH exome AF: 0.0249

GnomAD4 exome AF: 0.0269 AC: 38825 AN: 1441538 Hom.: 825 Cov.: 30 AF XY: 0.0276 AC XY: 19792 AN XY: 718364

African (AFR) AF: 0.00776 AC: 256 AN: 32992

American (AMR) AF: 0.0344 AC: 1536 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 293 AN: 25988

East Asian (EAS) AF: 0.112 AC: 4443 AN: 39618

South Asian (SAS) AF: 0.0514 AC: 4412 AN: 85802

European-Finnish (FIN) AF: 0.0207 AC: 1106 AN: 53400

Middle Eastern (MID) AF: 0.0235 AC: 134 AN: 5706

European-Non Finnish (NFE) AF: 0.0229 AC: 25011 AN: 1093626

Other (OTH) AF: 0.0274 AC: 1634 AN: 59718

GnomAD4 genome AF: 0.0232 AC: 3527 AN: 152298 Hom.: 74 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74470

African (AFR) AF: 0.00693 AC: 288 AN: 41554

American (AMR) AF: 0.0483 AC: 739 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.0900 AC: 467 AN: 5188

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4826

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1470 AN: 68034

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.0198 Hom.: 55

Bravo AF: 0.0234

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Glycogen storage disease, type VI (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		0.020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17123173; hg19: chr14-51387658;