dbSNP rs555929: AGL:c.2812+11G>A (chr1-99888119-G-A) – ACMG Classification: Benign (-20 pts)

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.2812+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,611,480 control chromosomes in the GnomAD database, including 385,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33533 hom., cov: 30)

Exomes 𝑓: 0.69 ( 352337 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.237

Publications

11 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: Laboratory for Molecular Medicine, ClinGen, Myriad Women's Health, Ambry Genetics, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

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=-0.85).

BP6

Variant 1-99888119-G-A is Benign according to our data. Variant chr1-99888119-G-A is described in ClinVar as Benign. ClinVar VariationId is 256730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 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	UniProt
AGL	NM_000642.3	MANE Select	c.2812+11G>A	intron	N/A	NP_000633.2	P35573-1
AGL	NM_000028.3		c.2812+11G>A	intron	N/A	NP_000019.2	P35573-1
AGL	NM_000643.3		c.2812+11G>A	intron	N/A	NP_000634.2	A0A0S2A4E4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGL	ENST00000361915.8	TSL:1 MANE Select	c.2812+11G>A	intron	N/A	ENSP00000355106.3	P35573-1
AGL	ENST00000294724.8	TSL:1	c.2812+11G>A	intron	N/A	ENSP00000294724.4	P35573-1
AGL	ENST00000370163.7	TSL:1	c.2812+11G>A	intron	N/A	ENSP00000359182.3	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100513

AN:

151778

Hom.:

33501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.686

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.700

Gnomad SAS

AF:

0.745

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.670

GnomAD2 exomes

AF:

0.690

AC:

173003

AN:

250574

AF XY:

0.693

show subpopulations

Gnomad AFR exome

AF:

0.585

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.682

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.690

GnomAD4 exome

AF:

0.694

AC:

1012703

AN:

1459582

Hom.:

352337

Cov.:

AF XY:

0.694

AC XY:

504198

AN XY:

726160

show subpopulations

African (AFR)

AF:

0.582

AC:

19432

AN:

33412

American (AMR)

AF:

0.719

AC:

32074

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

16110

AN:

26076

East Asian (EAS)

AF:

0.706

AC:

27960

AN:

39604

South Asian (SAS)

AF:

0.730

AC:

62909

AN:

86202

European-Finnish (FIN)

AF:

0.692

AC:

36545

AN:

52784

Middle Eastern (MID)

AF:

0.660

AC:

3798

AN:

5754

European-Non Finnish (NFE)

AF:

0.696

AC:

773055

AN:

1110812

Other (OTH)

AF:

0.677

AC:

40820

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15819

31638

47456

63275

79094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19638

39276

58914

78552

98190

<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:

0.662

AC:

100588

AN:

151898

Hom.:

33533

Cov.:

AF XY:

0.665

AC XY:

49355

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.582

AC:

24074

AN:

41396

American (AMR)

AF:

0.695

AC:

10607

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2081

AN:

3462

East Asian (EAS)

AF:

0.700

AC:

3614

AN:

5166

South Asian (SAS)

AF:

0.746

AC:

3580

AN:

4802

European-Finnish (FIN)

AF:

0.691

AC:

7295

AN:

10560

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47108

AN:

67936

Other (OTH)

AF:

0.675

AC:

1425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1721

3442

5162

6883

8604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.673

Hom.:

22183

Bravo

AF:

0.655

Asia WGS

AF:

0.730

AC:

2540

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease type III (4)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.032

(source)

DANN

Benign

0.32

PhyloP100

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over