ClinVar Genomic variation as it relates to human health
NM_024989.4(PGAP1):c.331A>G (p.Lys111Glu)
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_024989.4(PGAP1):c.331A>G (p.Lys111Glu)
Variation ID: 436297 Accession: VCV000436297.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q33.1 2: 196916564 (GRCh38) [ NCBI UCSC ] 2: 197781288 (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 Aug 28, 2017 Apr 15, 2024 Sep 23, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024989.4:c.331A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_079265.2:p.Lys111Glu missense NM_001321099.2:c.-192A>G 5 prime UTR NM_001321100.2:c.-781A>G 5 prime UTR NC_000002.12:g.196916564T>C NC_000002.11:g.197781288T>C NG_046780.1:g.15432A>G - Protein change
- K111E
- Other names
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- Canonical SPDI
- NC_000002.12:196916563:T: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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0.00080 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00115
Exome Aggregation Consortium (ExAC) 0.00070
The Genome Aggregation Database (gnomAD) 0.00077
Trans-Omics for Precision Medicine (TOPMed) 0.00080
The Genome Aggregation Database (gnomAD), exomes 0.00084
1000 Genomes Project 30x 0.00078
1000 Genomes Project 0.00080
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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PGAP1 | - | - |
GRCh38 GRCh37 |
378 | 416 |
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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Jun 8, 2016 | RCV000500227.7 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Sep 23, 2022 | RCV000705226.11 | |
Uncertain significance (3) |
criteria provided, single submitter
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Jun 1, 2016 | RCV000997638.19 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 10, 2021 | RCV001848874.5 |
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
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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
(Jun 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000596405.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Uncertain significance
(Nov 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Mental retardation, autosomal recessive 42
Affected status: unknown
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448968.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Seizures (present) , Dystonia (present) , Spasticity (present) , Migraine (present) , Abnormality of the cerebral white matter (present) , Dysarthria (present) , Mutism (present) … (more)
Seizures (present) , Dystonia (present) , Spasticity (present) , Migraine (present) , Abnormality of the cerebral white matter (present) , Dysarthria (present) , Mutism (present) , Hypermetropia (present) , Abnormality of skin pigmentation (present) , Anemia (present) , Generalized muscle weakness (present) , Language impairment (present) (less)
Sex: female
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Uncertain significance
(Jan 15, 2019)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal recessive 42
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001520817.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Uncertain significance
(Nov 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002105461.1
First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022 |
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Uncertain significance
(Mar 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal recessive 42
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002783851.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Sep 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal recessive 42
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000834213.5
First in ClinVar: Oct 10, 2018 Last updated: Nov 11, 2023 |
Comment:
This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 111 of the PGAP1 protein … (more)
This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 111 of the PGAP1 protein (p.Lys111Glu). This variant is present in population databases (rs142320636, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436297). 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 PGAP1 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 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: SCV001153258.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979454.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980070.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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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 rs142320636 ...
HelpRecord last updated Apr 15, 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.