ClinVar Genomic variation as it relates to human health
NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000642.3(AGL):c.4529dup (p.Tyr1510Ter)
Variation ID: 1094 Accession: VCV000001094.17
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 1p21.2 1: 99921580-99921581 (GRCh38) [ NCBI UCSC ] 1: 100387136-100387137 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 5, 2014 Feb 20, 2024 Dec 19, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000642.3:c.4529dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000633.2:p.Tyr1510Ter nonsense NM_000642.3:c.4529dupA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
nonsense NM_000028.3:c.4529dup NP_000019.2:p.Tyr1510Terfs frameshift nonsense NM_000642.2:c.4529dup NM_000643.3:c.4529dup NP_000634.2:p.Tyr1510Terfs frameshift nonsense NM_000644.3:c.4529dup NP_000635.2:p.Tyr1510Terfs frameshift nonsense NM_000646.3:c.4481dup NP_000637.2:p.Tyr1494Terfs frameshift nonsense NM_001425325.1:c.4529dup NP_001412254.1:p.Tyr1510Terfs frameshift nonsense NM_001425326.1:c.4508dup NP_001412255.1:p.Tyr1503Terfs frameshift nonsense NM_001425327.1:c.4328dup NP_001412256.1:p.Tyr1443Terfs frameshift nonsense NM_001425328.1:c.4325dup NP_001412257.1:p.Tyr1442Terfs frameshift nonsense NM_001425329.1:c.4190dup NP_001412258.1:p.Tyr1397Terfs frameshift nonsense NM_001425332.1:c.4151dup NP_001412261.1:p.Tyr1384Terfs frameshift nonsense NC_000001.11:g.99921581dup NC_000001.10:g.100387137dup NG_012865.1:g.76498dup - Protein change
- Y1510*, Y1494*
- Other names
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- Canonical SPDI
- NC_000001.11:99921580:A:AA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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AGL | - | - |
GRCh38 GRCh37 |
2646 | 2665 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
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Jan 6, 2017 | RCV000001152.4 | |
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Dec 19, 2023 | RCV000169573.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 1, 2016 | RCV001265666.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 06, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease IIIa
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697534.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
Comment:
Variant summary: The AGL c.4529dupA (p.Tyr1510X) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense … (more)
Variant summary: The AGL c.4529dupA (p.Tyr1510X) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121034 (1/60517), which does not exceed the estimated maximal expected allele frequency for a pathogenic AGL variant of 1/438. Multiple publications have cited the variant in affected individuals, who were homozygous and compound heterozygous. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003816708.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002055514.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
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Likely pathogenic
(Jan 23, 2015)
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criteria provided, single submitter
Method: literature only
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Glycogen storage disease type III
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000221073.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Likely pathogenic
(Jul 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811460.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Mar 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001443833.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Caucasian/African American
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Pathogenic
(Jun 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004212970.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000752145.5
First in ClinVar: Mar 29, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1510*) in the AGL gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Tyr1510*) in the AGL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the AGL protein. This variant is present in population databases (rs756759628, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with glycogen storage disease type III (PMID: 8990006, 20071996, 20490926, 23430490). ClinVar contains an entry for this variant (Variation ID: 1094). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 01, 1997)
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no assertion criteria provided
Method: literature only
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GLYCOGEN STORAGE DISEASE, TYPE IIIa
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021302.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 23, 2020 |
Comment on evidence:
In a child with an unusually severe phenotype of glycogen storage disease type IIIa (GSD3A; 232400) manifested in both liver and muscle, Shen et al. … (more)
In a child with an unusually severe phenotype of glycogen storage disease type IIIa (GSD3A; 232400) manifested in both liver and muscle, Shen et al. (1997) identified a homozygous 1-bp insertion (4529insA) in the 3-prime coding region of the AGL gene. The mutation created a termination codon at residue 1510 of their sequence. (They stated that amino acid residue 1510 in their study corresponded to residue 1493 of the Yang et al. (1992) sequence.) The child had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly, and died at 4 years of age. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001460668.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV002072438.2
First in ClinVar: Jan 29, 2022 Last updated: Oct 01, 2022 |
Comment:
Associated with more severe phenotype
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Glycogen Storage Disease Type III. | Adam MP | - | 2022 | PMID: 20301788 |
Mutation Analysis in Glycogen Storage Disease Type III Patients in the Netherlands: Novel Genotype-Phenotype Relationships and Five Novel Mutations in the AGL Gene. | Sentner CP | JIMD reports | 2013 | PMID: 23430490 |
Bulbar muscle weakness and fatty lingual infiltration in glycogen storage disorder type IIIa. | Horvath JJ | Molecular genetics and metabolism | 2012 | PMID: 23062577 |
Molecular analysis of the AGL gene: identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III. | Goldstein JL | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20648714 |
Glycogen storage disease type III in the Irish population. | Crushell E | Journal of inherited metabolic disease | 2010 | PMID: 20490926 |
The electrodiagnostic characteristics of Glycogen Storage Disease Type III. | Hobson-Webb LD | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20071996 |
Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions. | Cheng A | Human molecular genetics | 2009 | PMID: 19299494 |
A nonsense mutation due to a single base insertion in the 3'-coding region of glycogen debranching enzyme gene associated with a severe phenotype in a patient with glycogen storage disease type IIIa. | Shen J | Human mutation | 1997 | PMID: 8990006 |
Yang, B.-Z., Ding, J.-H., Bao, Y., Eason, J. F. M., Chen, Y.-T. Molecular basis of the enzymatic variability in type III glycogen storage disease (GSD-III). (Abstract) Am. J. Hum. Genet. 51 (suppl.): A28, 1992. | - | - | - | - |
Text-mined citations for rs387906244 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.