rs28730706

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000642.3(AGL):c.3849T>C(p.Ala1283Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,613,776 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 27 hom., cov: 33)

Exomes 𝑓: 0.013 ( 167 hom. )

Consequence

AGL
NM_000642.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.28

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-99912417-T-C is Benign according to our data. Variant chr1-99912417-T-C is described in ClinVar as Benign. ClinVar VariationId is 256745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0131 (2001/152334) while in subpopulation NFE AF = 0.0162 (1099/68032). AF 95% confidence interval is 0.0154. There are 27 homozygotes in GnomAd4. There are 1008 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3 link	c.3849T>C	p.Ala1283Ala	synonymous_variant	Exon 29 of 34	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8 link	c.3849T>C	p.Ala1283Ala	synonymous_variant	Exon 29 of 34	1	NM_000642.3	ENSP00000355106.3

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2004

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.0137

AC:

3452

AN:

251234

AF XY:

0.0138

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0344

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0132

AC:

19328

AN:

1461442

Hom.:

167

Cov.:

AF XY:

0.0133

AC XY:

9652

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.00302

AC:

101

AN:

33478

American (AMR)

AF:

0.00738

AC:

330

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0290

AC:

757

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39660

South Asian (SAS)

AF:

0.00451

AC:

389

AN:

86252

European-Finnish (FIN)

AF:

0.0348

AC:

1859

AN:

53392

Middle Eastern (MID)

AF:

0.0444

AC:

256

AN:

5764

European-Non Finnish (NFE)

AF:

0.0133

AC:

14742

AN:

1111698

Other (OTH)

AF:

0.0148

AC:

892

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

899

1798

2696

3595

4494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.0131

AC:

2001

AN:

152334

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1008

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41590

American (AMR)

AF:

0.0141

AC:

216

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00435

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0363

AC:

385

AN:

10600

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1099

AN:

68032

Other (OTH)

AF:

0.0208

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

194

292

389

486

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:

0.0145

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0167

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AGL: BP4, BP7, BS1, BS2 -

Mar 14, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 31, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Glycogen storage disease type III

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.0

(source)

DANN

Benign

0.61

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=90/10

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