ClinVar Genomic variation as it relates to human health
NM_000282.4(PCCA):c.1353+5_1353+9del
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.
Pathogenic(2); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000282.4(PCCA):c.1353+5_1353+9del
Variation ID: 254165 Accession: VCV000254165.6
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 13q32.3 13: 100307262-100307266 (GRCh38) [ NCBI UCSC ] 13: 100959516-100959520 (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 Feb 14, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000282.4:c.1353+5_1353+9del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_000282.3:c.1353+5_1353+9delGTTTA NM_001127692.3:c.1275+5_1275+9del splice donor NM_001178004.2:c.1353+5_1353+9del splice donor NM_001352605.2:c.1353+5_1353+9del splice donor NM_001352606.2:c.1209+5_1209+9del splice donor NM_001352607.2:c.1275+5_1275+9del splice donor NM_001352608.2:c.1131+5_1131+9del splice donor NM_001352609.2:c.1353+5_1353+9del splice donor NM_001352610.2:c.408+5_408+9del splice donor NM_001352611.2:c.408+5_408+9del splice donor NM_001352612.2:c.264+5_264+9del splice donor NC_000013.11:g.100307265_100307269del NC_000013.10:g.100959519_100959523del NG_008768.1:g.223183_223187del - Protein change
- Other names
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- Canonical SPDI
- NC_000013.11:100307261:TTAGTTTA:TTA
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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
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The frequency of the allele represented by this VCV record.
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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
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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 (4) |
criteria provided, conflicting classifications
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Jan 29, 2024 | RCV000236383.7 |
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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Pathogenic
(Jan 01, 2012)
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criteria provided, single submitter
Method: research
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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: SCV000256846.2 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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Pathogenic
(Feb 17, 2021)
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criteria provided, single submitter
Method: research, in vitro
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Propionic acidemia
Affected status: yes, not applicable
Allele origin:
germline,
not applicable
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Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics
Accession: SCV001482005.1
First in ClinVar: Feb 27, 2021 Last updated: Feb 27, 2021 |
Comment:
PS3, PM2, PM3_supportive, PP3, PP4
Observation 1: Observation 2:
Method: minigene splicing assay
Result:
exon skipping, corresponding to r.1285_1353del (p.Val429_Lys451del)
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Likely pathogenic
(Sep 15, 2023)
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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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Baylor Genetics
Accession: SCV004202850.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Jan 29, 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: SCV003442770.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change falls in intron 15 of the PCCA gene. It does not directly change the encoded amino acid sequence of the PCCA protein. … (more)
This sequence change falls in intron 15 of the PCCA gene. It does not directly change the encoded amino acid sequence of the PCCA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs764045674, gnomAD 0.01%). This variant has been observed in individual(s) with propionic acidemia (PMID: 25636094, 27227689). ClinVar contains an entry for this variant (Variation ID: 254165). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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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 |
[Analysis of PCCA and PCCB gene mutations in patients with propionic acidemia]. | Chen Z | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2015 | PMID: 25636094 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs764045674 ...
HelpRecord last updated Feb 20, 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.