ClinVar Genomic variation as it relates to human health
NM_000282.4(PCCA):c.1676G>T (p.Trp559Leu)
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(3); Benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000282.4(PCCA):c.1676G>T (p.Trp559Leu)
Variation ID: 218258 Accession: VCV000218258.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q32.3 13: 100368504 (GRCh38) [ NCBI UCSC ] 13: 101020758 (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 Jul 24, 2016 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000282.4:c.1676G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000273.2:p.Trp559Leu missense NM_001127692.3:c.1598G>T NP_001121164.1:p.Trp533Leu missense NM_001178004.2:c.1676G>T NP_001171475.1:p.Trp559Leu missense NM_001352605.2:c.1676G>T NP_001339534.1:p.Trp559Leu missense NM_001352606.2:c.1532G>T NP_001339535.1:p.Trp511Leu missense NM_001352607.2:c.1598G>T NP_001339536.1:p.Trp533Leu missense NM_001352608.2:c.1454G>T NP_001339537.1:p.Trp485Leu missense NM_001352609.2:c.1676G>T NP_001339538.1:p.Trp559Leu missense NM_001352610.2:c.731G>T NP_001339539.1:p.Trp244Leu missense NM_001352611.2:c.731G>T NP_001339540.1:p.Trp244Leu missense NM_001352612.2:c.587G>T NP_001339541.1:p.Trp196Leu missense NR_148027.2:n.1788G>T non-coding transcript variant NR_148030.2:n.1788G>T non-coding transcript variant NC_000013.11:g.100368504G>T NC_000013.10:g.101020758G>T NG_008768.1:g.284422G>T P05165:p.Trp559Leu - Protein change
- W559L, W533L, W485L, W196L, W244L, W511L
- Other names
- -
- Canonical SPDI
- NC_000013.11:100368503:G: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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0.00519 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00088
Trans-Omics for Precision Medicine (TOPMed) 0.00193
The Genome Aggregation Database (gnomAD), exomes 0.00302
Exome Aggregation Consortium (ExAC) 0.00308
1000 Genomes Project 30x 0.00515
1000 Genomes Project 0.00519
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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PCCA | - | - |
GRCh38 GRCh37 |
1332 | 1451 |
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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Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000236220.22 | |
Benign (1) |
criteria provided, single submitter
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May 12, 2017 | RCV000611609.1 | |
Benign (1) |
criteria provided, single submitter
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Jan 1, 2023 | RCV003401094.4 |
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
(Mar 18, 2016)
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criteria provided, single submitter
Method: reference population
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Propionic acidemia
Affected status: unknown
Allele origin:
germline
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Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center
Accession: SCV000267435.1
First in ClinVar: May 24, 2017 Last updated: May 24, 2017 |
Number of individuals with the variant: 7
Age: 40-69 years
Ethnicity/Population group: East Asian
Geographic origin: South Korean
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Benign
(May 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730302.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Uncertain significance
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Propionic acidemia
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001139373.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Propionic acidemia
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000382017.3
First in ClinVar: Dec 06, 2016 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Uncertain significance
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Propionic acidemia
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001652763.1
First in ClinVar: May 28, 2021 Last updated: May 28, 2021 |
Sex: mixed
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Propionic acidemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000631900.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Benign
(Jan 01, 2023)
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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: SCV004135101.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
PCCA: BS1, BS2
Number of individuals with the variant: 1
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Uncertain significance
(Apr 17, 2020)
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no assertion criteria provided
Method: clinical testing
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Propionic acidemia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001463918.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Jan 01, 2012)
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Flagged submission
flagged submission
Method: research
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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Propionic Acidemia
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital
Study: ORGANIC ACIDURIAS
Accession: SCV000256849.1 First in ClinVar: Jul 24, 2016 Last updated: Jul 24, 2016 |
Number of individuals with the variant: 1
Age: 0-9 years
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes. | Gupta D | Genetic testing and molecular biomarkers | 2016 | PMID: 27227689 |
Mutation analysis of the propionyl-CoA carboxylase alpha-subunit gene in four Japanese patients with propionic acidaemia. | Ohura T | Journal of inherited metabolic disease | 1999 | PMID: 10518292 |
Text-mined citations for rs118169528 ...
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.