1-99910892-G-A

Variant names:

Variant summary

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

The NM_000642.3(AGL):c.3836+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,582,054 control chromosomes in the GnomAD database, including 199,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16725 hom., cov: 31)

Exomes 𝑓: 0.50 ( 183175 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.294

Publications

9 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=-0.92).

BP6

Variant 1-99910892-G-A is Benign according to our data. Variant chr1-99910892-G-A is described in ClinVar as Benign. ClinVar VariationId is 256744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGL	NM_000642.3	MANE Select	c.3836+45G>A	intron	N/A	NP_000633.2
AGL	NM_000028.3		c.3836+45G>A	intron	N/A	NP_000019.2
AGL	NM_000643.3		c.3836+45G>A	intron	N/A	NP_000634.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGL	ENST00000361915.8	TSL:1 MANE Select	c.3836+45G>A	intron	N/A	ENSP00000355106.3
AGL	ENST00000294724.8	TSL:1	c.3836+45G>A	intron	N/A	ENSP00000294724.4
AGL	ENST00000370163.7	TSL:1	c.3836+45G>A	intron	N/A	ENSP00000359182.3

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70337

AN:

151300

Hom.:

16702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.470

GnomAD2 exomes

AF:

0.482

AC:

115140

AN:

238790

AF XY:

0.474

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.543

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.478

GnomAD4 exome

AF:

0.502

AC:

718768

AN:

1430636

Hom.:

183175

Cov.:

AF XY:

0.497

AC XY:

354033

AN XY:

712122

show subpopulations

African (AFR)

AF:

0.370

AC:

12017

AN:

32496

American (AMR)

AF:

0.565

AC:

24652

AN:

43610

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

10000

AN:

25646

East Asian (EAS)

AF:

0.612

AC:

23533

AN:

38424

South Asian (SAS)

AF:

0.369

AC:

31154

AN:

84496

European-Finnish (FIN)

AF:

0.502

AC:

26093

AN:

51940

Middle Eastern (MID)

AF:

0.354

AC:

2007

AN:

5662

European-Non Finnish (NFE)

AF:

0.515

AC:

560979

AN:

1089410

Other (OTH)

AF:

0.481

AC:

28333

AN:

58952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

15478

30956

46433

61911

77389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16172

32344

48516

64688

80860

<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:

0.465

AC:

70402

AN:

151418

Hom.:

16725

Cov.:

AF XY:

0.463

AC XY:

34233

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.372

AC:

15379

AN:

41344

American (AMR)

AF:

0.509

AC:

7766

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1310

AN:

3462

East Asian (EAS)

AF:

0.569

AC:

2926

AN:

5140

South Asian (SAS)

AF:

0.377

AC:

1808

AN:

4798

European-Finnish (FIN)

AF:

0.502

AC:

5248

AN:

10448

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.509

AC:

34472

AN:

67682

Other (OTH)

AF:

0.475

AC:

998

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1907

3815

5722

7630

9537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.487

Hom.:

45472

Bravo

AF:

0.468

Asia WGS

AF:

0.477

AC:

1661

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

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

Glycogen storage disease type III

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.65

(source)

DANN

Benign

0.20

PhyloP100

-0.29

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over