Menu
GeneBe

1-99881185-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000642.3(AGL):​c.2001+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,570 control chromosomes in the GnomAD database, including 245,309 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20668 hom., cov: 31)
Exomes 𝑓: 0.55 ( 224641 hom. )

Consequence

AGL
NM_000642.3 splice_region, intron

Scores

2
Splicing: ADA: 0.00003241
2

Clinical Significance

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

Conservation

PhyloP100: 2.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 1-99881185-T-C is Benign according to our data. Variant chr1-99881185-T-C is described in ClinVar as [Benign]. Clinvar id is 256725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-99881185-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGLNM_000642.3 linkuse as main transcriptc.2001+8T>C splice_region_variant, intron_variant ENST00000361915.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGLENST00000361915.8 linkuse as main transcriptc.2001+8T>C splice_region_variant, intron_variant 1 NM_000642.3 P1P35573-1

Frequencies

GnomAD3 genomes
AF:
0.516
AC:
78283
AN:
151780
Hom.:
20631
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.425
Gnomad AMI
AF:
0.464
Gnomad AMR
AF:
0.565
Gnomad ASJ
AF:
0.419
Gnomad EAS
AF:
0.675
Gnomad SAS
AF:
0.599
Gnomad FIN
AF:
0.521
Gnomad MID
AF:
0.443
Gnomad NFE
AF:
0.547
Gnomad OTH
AF:
0.515
GnomAD3 exomes
AF:
0.554
AC:
139035
AN:
250904
Hom.:
39215
AF XY:
0.553
AC XY:
75041
AN XY:
135590
show subpopulations
Gnomad AFR exome
AF:
0.431
Gnomad AMR exome
AF:
0.622
Gnomad ASJ exome
AF:
0.423
Gnomad EAS exome
AF:
0.660
Gnomad SAS exome
AF:
0.589
Gnomad FIN exome
AF:
0.514
Gnomad NFE exome
AF:
0.544
Gnomad OTH exome
AF:
0.541
GnomAD4 exome
AF:
0.552
AC:
806886
AN:
1460672
Hom.:
224641
Cov.:
37
AF XY:
0.553
AC XY:
401532
AN XY:
726678
show subpopulations
Gnomad4 AFR exome
AF:
0.425
Gnomad4 AMR exome
AF:
0.612
Gnomad4 ASJ exome
AF:
0.432
Gnomad4 EAS exome
AF:
0.676
Gnomad4 SAS exome
AF:
0.590
Gnomad4 FIN exome
AF:
0.523
Gnomad4 NFE exome
AF:
0.552
Gnomad4 OTH exome
AF:
0.534
GnomAD4 genome
AF:
0.516
AC:
78361
AN:
151898
Hom.:
20668
Cov.:
31
AF XY:
0.518
AC XY:
38423
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.425
Gnomad4 AMR
AF:
0.565
Gnomad4 ASJ
AF:
0.419
Gnomad4 EAS
AF:
0.675
Gnomad4 SAS
AF:
0.600
Gnomad4 FIN
AF:
0.521
Gnomad4 NFE
AF:
0.547
Gnomad4 OTH
AF:
0.522
Alfa
AF:
0.533
Hom.:
16112
Bravo
AF:
0.515
Asia WGS
AF:
0.633
AC:
2202
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Glycogen storage disease type III Benign:4
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 02, 2015This 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. -
not provided Benign:1
Benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicOct 22, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
7.4
DANN
Benign
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000032
dbscSNV1_RF
Benign
0.0020
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3736296; hg19: chr1-100346741; COSMIC: COSV54049713; COSMIC: COSV54049713; API