ClinVar Genomic variation as it relates to human health
NM_000642.3(AGL):c.256C>T (p.Gln86Ter)
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.256C>T (p.Gln86Ter)
Variation ID: 196286 Accession: VCV000196286.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p21.2 1: 99861676 (GRCh38) [ NCBI UCSC ] 1: 100327232 (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 Dec 26, 2017 Feb 20, 2024 Jan 21, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000642.3:c.256C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000633.2:p.Gln86Ter nonsense NM_000028.3:c.256C>T NP_000019.2:p.Gln86Ter nonsense NM_000643.3:c.256C>T NP_000634.2:p.Gln86Ter nonsense NM_000644.3:c.256C>T NP_000635.2:p.Gln86Ter nonsense NM_000646.3:c.208C>T NP_000637.2:p.Gln70Ter nonsense NM_001425325.1:c.256C>T NP_001412254.1:p.Gln86Ter nonsense NM_001425326.1:c.256C>T NP_001412255.1:p.Gln86Ter nonsense NM_001425327.1:c.256C>T NP_001412256.1:p.Gln86Ter nonsense NM_001425328.1:c.256C>T NP_001412257.1:p.Gln86Ter nonsense NM_001425329.1:c.256C>T NP_001412258.1:p.Gln86Ter nonsense NC_000001.11:g.99861676C>T NC_000001.10:g.100327232C>T NG_012865.1:g.16593C>T - Protein change
- Q86*, Q70*
- Other names
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- Canonical SPDI
- NC_000001.11:99861675:C:T
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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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0.00020 (T)
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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 0.00005
The Genome Aggregation Database (gnomAD) 0.00014
Trans-Omics for Precision Medicine (TOPMed) 0.00015
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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
Help
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/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 21, 2024 | RCV000177086.20 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 25, 2017 | RCV000588509.1 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 23, 2021 | RCV000724625.7 |
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
(Aug 25, 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: SCV000697531.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The AGL c.256C>T (p.Gln86X) 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.256C>T (p.Gln86X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.3216_3217delGA (p.Glu1072fsX36) and c.4529dupA (p.Tyr1510X)). This variant was found in 3/121018 control chromosomes at a frequency of 0.0000248, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGL variant (0.0022822). Multiple publications have cited the variant in affected individuals. In addition, a clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Mar 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000228908.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely pathogenic
(Feb 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000890327.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 20648714, 22899091, 10655153, 31589614) (less)
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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: SCV002055465.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
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Pathogenic
(Sep 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002572519.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). This stop-gained (nonsense) variant is predicted to … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.007%). This stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000196286 / PMID: 10655153). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hepatomegaly (present) , Elevated circulating hepatic transaminase concentration (present) , Short stature (present) , Doll-like facies (present)
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Likely pathogenic
(Jun 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004013290.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
PVS1, PM2
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Likely pathogenic
(May 20, 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: SCV003832506.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 21, 2024)
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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: SCV000626700.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln86*) in the AGL gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln86*) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is present in population databases (rs193186112, gnomAD 0.07%). This premature translational stop signal has been observed in individuals with glycogen storage disease (PMID: 10655153, 20648714, 22899091). ClinVar contains an entry for this variant (Variation ID: 196286). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501776.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Apr 06, 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:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893164.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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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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RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin. | Wang J | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22899091 |
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 |
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 |
Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. | Shaiu WL | Molecular genetics and metabolism | 2000 | PMID: 10655153 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AGL | - | - | - | - |
Text-mined citations for rs193186112 ...
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.