dbSNP rs834575: AGL:c.3700+32T>C (chr1-99902826-T-C) – 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.3700+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,507,456 control chromosomes in the GnomAD database, including 1,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 257 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1512 hom. )

Consequence

AGL
NM_000642.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.243

Publications

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

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=-0.83).

BP6

Variant 1-99902826-T-C is Benign according to our data. Variant chr1-99902826-T-C is described in ClinVar as Benign. ClinVar VariationId is 256742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0774 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.3700+32T>C	intron	N/A	NP_000633.2	P35573-1
AGL	NM_000028.3		c.3700+32T>C	intron	N/A	NP_000019.2	P35573-1
AGL	NM_000643.3		c.3700+32T>C	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.3700+32T>C	intron	N/A	ENSP00000355106.3	P35573-1
AGL	ENST00000294724.8	TSL:1	c.3700+32T>C	intron	N/A	ENSP00000294724.4	P35573-1
AGL	ENST00000370163.7	TSL:1	c.3700+32T>C	intron	N/A	ENSP00000359182.3	P35573-1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7943

AN:

152152

Hom.:

257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0388

AC:

9382

AN:

241516

AF XY:

0.0389

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00496

Gnomad FIN exome

AF:

0.0536

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0448

AC:

60647

AN:

1355186

Hom.:

1512

Cov.:

AF XY:

0.0445

AC XY:

30205

AN XY:

679508

show subpopulations

African (AFR)

AF:

0.0840

AC:

2625

AN:

31232

American (AMR)

AF:

0.0168

AC:

734

AN:

43712

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

296

AN:

25338

East Asian (EAS)

AF:

0.0313

AC:

1222

AN:

39010

South Asian (SAS)

AF:

0.0441

AC:

3687

AN:

83618

European-Finnish (FIN)

AF:

0.0535

AC:

2822

AN:

52718

Middle Eastern (MID)

AF:

0.0236

AC:

130

AN:

5516

European-Non Finnish (NFE)

AF:

0.0460

AC:

46821

AN:

1017340

Other (OTH)

AF:

0.0407

AC:

2310

AN:

56702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2779

5558

8336

11115

13894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1692

3384

5076

6768

8460

<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:

0.0522

AC:

7941

AN:

152270

Hom.:

257

Cov.:

AF XY:

0.0514

AC XY:

3828

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0796

AC:

3307

AN:

41530

American (AMR)

AF:

0.0300

AC:

458

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.0158

AC:

AN:

5188

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4828

European-Finnish (FIN)

AF:

0.0560

AC:

595

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0457

AC:

3111

AN:

68030

Other (OTH)

AF:

0.0430

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

380

760

1140

1520

1900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0465

Hom.:

Bravo

AF:

0.0486

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Glycogen storage disease type III (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.22

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over