rs11807956
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000642.3(AGL):c.3619G>A(p.Ala1207Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00157 in 1,613,444 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0085 ( 23 hom., cov: 32)
Exomes 𝑓: 0.00085 ( 20 hom. )
Consequence
AGL
NM_000642.3 missense
NM_000642.3 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 4.02
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006166458).
BP6
?
Variant 1-99902713-G-A is Benign according to our data. Variant chr1-99902713-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 256741.We mark this variant Likely_benign, oryginal submissions are: {Benign=5, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00848 (1291/152284) while in subpopulation AFR AF= 0.0299 (1242/41560). AF 95% confidence interval is 0.0285. There are 23 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.3619G>A | p.Ala1207Thr | missense_variant | 27/34 | ENST00000361915.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGL | ENST00000361915.8 | c.3619G>A | p.Ala1207Thr | missense_variant | 27/34 | 1 | NM_000642.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00846 AC: 1287AN: 152166Hom.: 23 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00221 AC: 555AN: 250652Hom.: 11 AF XY: 0.00149 AC XY: 202AN XY: 135626
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GnomAD4 exome AF: 0.000847 AC: 1238AN: 1461160Hom.: 20 Cov.: 30 AF XY: 0.000721 AC XY: 524AN XY: 726906
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GnomAD4 genome ? AF: 0.00848 AC: 1291AN: 152284Hom.: 23 Cov.: 32 AF XY: 0.00802 AC XY: 597AN XY: 74472
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ExAC
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disease type III Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 02, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2017 | 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 | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 22, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;.;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
B;B;B;B;B
Vest4
MVP
MPC
0.053
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at