ClinVar Genomic variation as it relates to human health
NM_000642.3(AGL):c.4283A>C (p.Tyr1428Ser)
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.4283A>C (p.Tyr1428Ser)
Variation ID: 424905 Accession: VCV000424905.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p21.2 1: 99916433 (GRCh38) [ NCBI UCSC ] 1: 100381989 (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 8, 2017 May 12, 2024 Jun 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000642.3:c.4283A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000633.2:p.Tyr1428Ser missense NM_000028.3:c.4283A>C NP_000019.2:p.Tyr1428Ser missense NM_000643.3:c.4283A>C NP_000634.2:p.Tyr1428Ser missense NM_000644.3:c.4283A>C NP_000635.2:p.Tyr1428Ser missense NM_000646.3:c.4235A>C NP_000637.2:p.Tyr1412Ser missense NM_001425325.1:c.4283A>C NP_001412254.1:p.Tyr1428Ser missense NM_001425326.1:c.4262A>C NP_001412255.1:p.Tyr1421Ser missense NM_001425327.1:c.4082A>C NP_001412256.1:p.Tyr1361Ser missense NM_001425328.1:c.4079A>C NP_001412257.1:p.Tyr1360Ser missense NM_001425329.1:c.3944A>C NP_001412258.1:p.Tyr1315Ser missense NM_001425332.1:c.3905A>C NP_001412261.1:p.Tyr1302Ser missense NC_000001.11:g.99916433A>C NC_000001.10:g.100381989A>C NG_012865.1:g.71350A>C - Protein change
- Y1428S, Y1412S, Y1302S, Y1315S, Y1360S, Y1361S, Y1421S
- Other names
- p.Tyr1428Ser
- Canonical SPDI
- NC_000001.11:99916432:A:C
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
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 |
2647 | 2666 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Dec 1, 2016 | RCV000488240.18 | |
Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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Jun 24, 2023 | RCV000525633.9 |
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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Uncertain significance
(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: SCV002055454.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
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Uncertain significance
(Oct 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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Invitae
Accession: SCV000626751.2
First in ClinVar: Dec 26, 2017 Last updated: Mar 26, 2023 |
Comment:
This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 1428 of the AGL protein (p.Tyr1428Ser). … (more)
This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 1428 of the AGL protein (p.Tyr1428Ser). This variant is present in population databases (rs150532164, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 424905). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AGL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(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: SCV004041185.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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Uncertain significance
(May 21, 2021)
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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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Clinical Genomics Program, Stanford Medicine
Accession: SCV004801384.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
• The p.Tyr1428Ser variant in the AGL gene has not been previously reported in association with disease. • This variant has been identified in 4/281,644 … (more)
• The p.Tyr1428Ser variant in the AGL gene has not been previously reported in association with disease. • This variant has been identified in 4/281,644 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. • Computational tools predict that this variant is deleterious; however, the accuracy of in silico algorithms is limited. • These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Tyr1428Ser variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; PP3] (less)
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Uncertain significance
(Dec 01, 2016)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000574778.27
First in ClinVar: May 08, 2017 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(Mar 04, 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: SCV002094583.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs150532164 ...
HelpRecord last updated May 12, 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.