rs41317304

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002863.5(PYGL):c.529-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,610,916 control chromosomes in the GnomAD database, including 1,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 379 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1340 hom. )

Consequence

PYGL
NM_002863.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.519

Publications

4 publications found

Variant links:

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

PYGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 14-50924122-C-T is Benign according to our data. Variant chr14-50924122-C-T is described in ClinVar as Benign. ClinVar VariationId is 258845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYGL	NM_002863.5 link	c.529-22G>A		intron_variant	Intron 4 of 19	ENST00000216392.8	NP_002854.3	P06737-1
PYGL	NM_001163940.2 link	c.427-22G>A		intron_variant	Intron 3 of 18		NP_001157412.1	P06737-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYGL	ENST00000216392.8 link	c.529-22G>A	intron_variant	Intron 4 of 19	1	NM_002863.5	ENSP00000216392.7	P06737-1
PYGL	ENST00000532462.5 link	c.529-22G>A	intron_variant	Intron 4 of 19	1		ENSP00000431657.1	E9PK47
PYGL	ENST00000530336.2 link	n.596-22G>A	intron_variant	Intron 4 of 4	1
PYGL	ENST00000544180.6 link	c.427-22G>A	intron_variant	Intron 3 of 18	2		ENSP00000443787.1	P06737-2

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

8961

AN:

152056

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0403

AC:

10123

AN:

251058

AF XY:

0.0402

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0534

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0357

GnomAD4 exome

AF:

0.0383

AC:

55829

AN:

1458742

Hom.:

1340

Cov.:

AF XY:

0.0384

AC XY:

27870

AN XY:

725874

show subpopulations

African (AFR)

AF:

0.123

AC:

4091

AN:

33364

American (AMR)

AF:

0.0185

AC:

829

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

923

AN:

26094

East Asian (EAS)

AF:

0.000202

AC:

AN:

39642

South Asian (SAS)

AF:

0.0395

AC:

3405

AN:

86208

European-Finnish (FIN)

AF:

0.0503

AC:

2672

AN:

53110

Middle Eastern (MID)

AF:

0.0549

AC:

316

AN:

5756

European-Non Finnish (NFE)

AF:

0.0371

AC:

41216

AN:

1109608

Other (OTH)

AF:

0.0393

AC:

2369

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2451

4903

7354

9806

12257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1492

2984

4476

5968

7460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0589

AC:

8965

AN:

152174

Hom.:

379

Cov.:

AF XY:

0.0587

AC XY:

4369

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.119

AC:

4934

AN:

41478

American (AMR)

AF:

0.0243

AC:

371

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

115

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0307

AC:

148

AN:

4828

European-Finnish (FIN)

AF:

0.0551

AC:

584

AN:

10598

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0397

AC:

2700

AN:

68012

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

444

887

1331

1774

2218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0499

Hom.:

Bravo

AF:

0.0583

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 21, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 12, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.6

(source)

DANN

Benign

0.77

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over