ClinVar Genomic variation as it relates to human health
NM_001351132.2(PEX5):c.496C>G (p.Gln166Glu)
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_001351132.2(PEX5):c.496C>G (p.Gln166Glu)
Variation ID: 449585 Accession: VCV000449585.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 12p13.31 12: 7199058 (GRCh38) [ NCBI UCSC ] 12: 7351654 (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 19, 2017 May 1, 2024 Aug 21, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001351132.2:c.496C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001338061.1:p.Gln166Glu missense NM_000319.5:c.496C>G NP_000310.2:p.Gln166Glu missense NM_001131023.2:c.541C>G NP_001124495.1:p.Gln181Glu missense NM_001131024.2:c.496C>G NP_001124496.1:p.Gln166Glu missense NM_001131025.2:c.496C>G NP_001124497.1:p.Gln166Glu missense NM_001131026.2:c.496C>G NP_001124498.1:p.Gln166Glu missense NM_001300789.3:c.496C>G NP_001287718.2:p.Gln166Glu missense NM_001351124.3:c.496C>G NP_001338053.1:p.Gln166Glu missense NM_001351126.2:c.496C>G NP_001338055.1:p.Gln166Glu missense NM_001351127.2:c.496C>G NP_001338056.1:p.Gln166Glu missense NM_001351128.2:c.496C>G NP_001338057.1:p.Gln166Glu missense NM_001351130.3:c.496C>G NP_001338059.1:p.Gln166Glu missense NM_001351131.2:c.496C>G NP_001338060.1:p.Gln166Glu missense NM_001351133.2:c.496C>G NP_001338062.1:p.Gln166Glu missense NM_001351134.2:c.496C>G NP_001338063.1:p.Gln166Glu missense NM_001351135.3:c.541C>G NP_001338064.2:p.Gln181Glu missense NM_001351136.2:c.496C>G NP_001338065.1:p.Gln166Glu missense NM_001351137.3:c.496C>G NP_001338066.2:p.Gln166Glu missense NM_001351138.2:c.541C>G NP_001338067.1:p.Gln181Glu missense NM_001351139.2:c.496C>G NP_001338068.1:p.Gln166Glu missense NM_001351140.2:c.496C>G NP_001338069.1:p.Gln166Glu missense NM_001374645.1:c.496C>G NP_001361574.1:p.Gln166Glu missense NM_001374646.1:c.496C>G NP_001361575.1:p.Gln166Glu missense NM_001374647.2:c.496C>G NP_001361576.1:p.Gln166Glu missense NM_001374648.2:c.496C>G NP_001361577.1:p.Gln166Glu missense NM_001374649.2:c.496C>G NP_001361578.1:p.Gln166Glu missense NC_000012.12:g.7199058C>G NC_000012.11:g.7351654C>G NG_008448.1:g.14896C>G - Protein change
- Q166E, Q181E
- Other names
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- Canonical SPDI
- NC_000012.12:7199057:C:G
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00007
The Genome Aggregation Database (gnomAD), exomes 0.00008
Exome Aggregation Consortium (ExAC) 0.00010
The Genome Aggregation Database (gnomAD) 0.00011
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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PEX5 | - | - |
GRCh38 GRCh38 GRCh37 |
988 | 1039 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Jan 11, 2018 | RCV000726787.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 16, 2018 | RCV001109086.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 2, 2021 | RCV002527582.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 21, 2022 | RCV001067078.4 |
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
(Jan 11, 2018)
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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: SCV000703028.2
First in ClinVar: Dec 19, 2017 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Nov 11, 2015)
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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: SCV000617887.2
First in ClinVar: Dec 19, 2017 Last updated: Apr 17, 2019 |
Comment:
The Q166E variant in the PEX5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The Q166E variant in the PEX5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q166E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q166E variant is a semi-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Q166E as a variant of uncertain significance. (less)
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Uncertain significance
(Mar 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 2A (Zellweger)
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001266394.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Aug 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 2B
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001232112.4
First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 166 of the PEX5 protein … (more)
This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 166 of the PEX5 protein (p.Gln166Glu). This variant is present in population databases (rs751043763, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PEX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 449585). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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
(Aug 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003705122.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.496C>G (p.Q166E) alteration is located in exon 6 (coding exon 5) of the PEX5 gene. This alteration results from a C to G substitution … (more)
The c.496C>G (p.Q166E) alteration is located in exon 6 (coding exon 5) of the PEX5 gene. This alteration results from a C to G substitution at nucleotide position 496, causing the glutamine (Q) at amino acid position 166 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PEX5 | - | - | - | - |
Text-mined citations for rs751043763 ...
HelpRecord last updated May 01, 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.