chr1-99896267-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000642.3(AGL):c.3260-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,568,336 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 28 hom., cov: 32)

Exomes 𝑓: 0.013 ( 159 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.19

Publications

1 publications found

Variant links:

Genes affected

AGL (HGNC:321): (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) This gene encodes the glycogen debrancher enzyme which is involved in glycogen degradation. This enzyme has two independent catalytic activities which occur at different sites on the protein: a 4-alpha-glucotransferase activity and a amylo-1,6-glucosidase activity. Mutations in this gene are associated with glycogen storage disease although a wide range of enzymatic and clinical variability occurs which may be due to tissue-specific alternative splicing. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

AGL Gene-Disease associations (from GenCC):

glycogen storage disease III
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Laboratory for Molecular Medicine, Myriad Women’s Health, Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

AGL 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=-0.63).

BP6

Variant 1-99896267-G-A is Benign according to our data. Variant chr1-99896267-G-A is described in ClinVar as Benign. ClinVar VariationId is 256736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0128 (1951/152212) while in subpopulation NFE AF = 0.0155 (1052/68004). AF 95% confidence interval is 0.0147. There are 28 homozygotes in GnomAd4. There are 989 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3 link	c.3260-19G>A		intron_variant	Intron 24 of 33	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 link	c.3260-19G>A		intron_variant	Intron 24 of 33	1	NM_000642.3	ENSP00000355106.3

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1953

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0366

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0135

AC:

3401

AN:

251388

AF XY:

0.0136

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00648

Gnomad ASJ exome

AF:

0.0285

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0343

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0127

AC:

17917

AN:

1416124

Hom.:

159

Cov.:

AF XY:

0.0127

AC XY:

9015

AN XY:

707360

show subpopulations

African (AFR)

AF:

0.00287

AC:

AN:

32412

American (AMR)

AF:

0.00737

AC:

329

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

745

AN:

25850

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39422

South Asian (SAS)

AF:

0.00422

AC:

360

AN:

85290

European-Finnish (FIN)

AF:

0.0348

AC:

1858

AN:

53332

Middle Eastern (MID)

AF:

0.0446

AC:

254

AN:

5692

European-Non Finnish (NFE)

AF:

0.0125

AC:

13436

AN:

1070662

Other (OTH)

AF:

0.0143

AC:

841

AN:

58796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

872

1744

2616

3488

4360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.0128

AC:

1951

AN:

152212

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

989

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00243

AC:

101

AN:

41536

American (AMR)

AF:

0.0142

AC:

218

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00435

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0366

AC:

387

AN:

10580

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1052

AN:

68004

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

200

300

400

500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0194

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 31, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 14, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 10, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease type III

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.63

CADD

Benign

7.2

(source)

DANN

Benign

0.53

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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