ClinVar Genomic variation as it relates to human health
NM_198681.4(PLEKHG5):c.-120C>T
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.
Uncertain significance(2); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_198681.4(PLEKHG5):c.-120C>T
Variation ID: 1050168 Accession: VCV001050168.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.31 1: 6496525 (GRCh38) [ NCBI UCSC ] 1: 6556585 (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 Apr 13, 2021 May 12, 2024 Jan 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001042663.3:c.-9C>T 5 prime UTR NM_001265592.2:c.-9C>T 5 prime UTR NM_198681.4:c.-120C>T 5 prime UTR NC_000001.11:g.6496525G>A NC_000001.10:g.6556585G>A NG_007978.1:g.28485C>T LRG_262:g.28485C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000001.11:6496524:G:A
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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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0.00060 (A)
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Allele frequency
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The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00078
Exome Aggregation Consortium (ExAC) 0.00143
Trans-Omics for Precision Medicine (TOPMed) 0.00190
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00307
- Links
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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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PLEKHG5 | - | - |
GRCh38 GRCh37 |
1318 | 1427 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jan 1, 2024 | RCV001357159.24 | |
Uncertain significance (1) |
no assertion criteria provided
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- | RCV002271226.8 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 13, 2020 | RCV003918882.1 |
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
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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
(Aug 20, 2021)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002050196.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
The PLEKHG5 c.112C>T, p.Pro38Ser (rs201669114), is reported in the literature in 4 individuals in 2 families affected with Alzheimer’s disease (Cukier, 2017), but has not … (more)
The PLEKHG5 c.112C>T, p.Pro38Ser (rs201669114), is reported in the literature in 4 individuals in 2 families affected with Alzheimer’s disease (Cukier, 2017), but has not been reported in patients affected with Charcot-Marie-Tooth disease. This variant is found in the general population with an allele frequency of 0.13% (362/271,658 alleles, including 1 homozygote) in the Genome Aggregation Database. The proline at codon 38 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, the clinical significance of this variant is uncertain at this time. (less)
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Uncertain significance
(Apr 13, 2022)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001712957.2
First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024 |
Comment:
BP4
Number of individuals with the variant: 8
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Likely benign
(Aug 13, 2020)
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criteria provided, single submitter
Method: clinical testing
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PLEKHG5-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004739688.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Jan 01, 2024)
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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: SCV004042413.6
First in ClinVar: Oct 14, 2023 Last updated: May 12, 2024 |
Comment:
PLEKHG5: BP4
Number of individuals with the variant: 2
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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:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552531.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The PLEKHG5 p.Pro40Ser variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs201669114) and … (more)
The PLEKHG5 p.Pro40Ser variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs201669114) and in control databases in 362 of 271658 chromosomes (1 homozygous) at a frequency of 0.001333 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 304 of 123808 chromosomes (freq: 0.002455), Ashkenazi Jewish in 17 of 10068 chromosomes (freq: 0.001689), Other in 7 of 6866 chromosomes (freq: 0.00102), Latino in 19 of 34140 chromosomes (freq: 0.000557), European (Finnish) in 8 of 24888 chromosomes (freq: 0.000321), African in 6 of 23608 chromosomes (freq: 0.000254) and South Asian in 1 of 29698 chromosomes (freq: 0.000034), but was not observed in the East Asian population. The p.Pro40 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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Peripheral neuropathy
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Wuerzburg
Accession: SCV002553214.1
First in ClinVar: Jul 30, 2022 Last updated: Jul 30, 2022 |
Number of individuals with the variant: 1
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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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Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function. | Cukier HN | Journal of Alzheimer's disease & Parkinsonism | 2017 | PMID: 29177109 |
Text-mined citations for rs201669114 ...
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.