1-99861470-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000642.3(AGL):c.83-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,611,300 control chromosomes in the GnomAD database, including 28,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.24 ( 5046 hom., cov: 32)
Exomes 𝑓: 0.17 ( 23743 hom. )
Consequence
AGL
NM_000642.3 intron
NM_000642.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.01
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 1-99861470-C-T is Benign according to our data. Variant chr1-99861470-C-T is described in ClinVar as [Benign]. Clinvar id is 256750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-99861470-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.83-33C>T | intron_variant | ENST00000361915.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGL | ENST00000361915.8 | c.83-33C>T | intron_variant | 1 | NM_000642.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.235 AC: 35761AN: 151892Hom.: 5048 Cov.: 32
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GnomAD3 exomes AF: 0.184 AC: 45917AN: 249460Hom.: 4712 AF XY: 0.183 AC XY: 24724AN XY: 134856
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GnomAD4 exome AF: 0.175 AC: 254822AN: 1459290Hom.: 23743 Cov.: 33 AF XY: 0.175 AC XY: 127188AN XY: 725964
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GnomAD4 genome AF: 0.235 AC: 35761AN: 152010Hom.: 5046 Cov.: 32 AF XY: 0.234 AC XY: 17424AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glycogen storage disease type III Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at