1-99874669-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000642.3(AGL):c.959-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,597,686 control chromosomes in the GnomAD database, including 407,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.73 ( 41324 hom., cov: 32)
Exomes 𝑓: 0.71 ( 365682 hom. )
Consequence
AGL
NM_000642.3 intron
NM_000642.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.906
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=-0.96).
BP6
Variant 1-99874669-G-A is Benign according to our data. Variant chr1-99874669-G-A is described in ClinVar as [Benign]. Clinvar id is 256751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-99874669-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.959-18G>A | intron_variant | ENST00000361915.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGL | ENST00000361915.8 | c.959-18G>A | intron_variant | 1 | NM_000642.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.734 AC: 111364AN: 151696Hom.: 41276 Cov.: 32
GnomAD3 genomes
AF:
AC:
111364
AN:
151696
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.717 AC: 176020AN: 245452Hom.: 63332 AF XY: 0.717 AC XY: 95134AN XY: 132622
GnomAD3 exomes
AF:
AC:
176020
AN:
245452
Hom.:
AF XY:
AC XY:
95134
AN XY:
132622
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.710 AC: 1026190AN: 1445872Hom.: 365682 Cov.: 32 AF XY: 0.709 AC XY: 510548AN XY: 719644
GnomAD4 exome
AF:
AC:
1026190
AN:
1445872
Hom.:
Cov.:
32
AF XY:
AC XY:
510548
AN XY:
719644
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.734 AC: 111477AN: 151814Hom.: 41324 Cov.: 32 AF XY: 0.734 AC XY: 54466AN XY: 74198
GnomAD4 genome
AF:
AC:
111477
AN:
151814
Hom.:
Cov.:
32
AF XY:
AC XY:
54466
AN XY:
74198
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glycogen storage disease type III Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 29, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2015 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 08, 2016 | Variant summary: The AGL c.959-18G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. This variant was found in 84126/115018 control chromosomes (30465 homozygotes) at a frequency of 0.731416, which is approximately 320 times the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at