VCV002749726.1 - ClinVar

NM_000282.4(PCCA):c.1418_1419del (p.Tyr473fs)

Germline

Classification

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.

(1)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000282.4(PCCA):c.1418_1419del (p.Tyr473fs)

Variation ID: 2749726 Accession: VCV002749726.1

Type and length

Deletion, 2 bp

Location

Cytogenetic: 13q32.3 13: 100309896-100309897 (GRCh38) [ NCBI UCSC ] 13: 100962150-100962151 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Feb 14, 2024	Feb 14, 2024	Sep 30, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000282.4:c.1418_1419del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000273.2:p.Tyr473fs	frameshift
NM_001127692.3:c.1340_1341del	NP_001121164.1:p.Tyr447fs	frameshift
NM_001178004.2:c.1418_1419del	NP_001171475.1:p.Tyr473fs	frameshift
NM_001352605.2:c.1418_1419del	NP_001339534.1:p.Tyr473fs	frameshift
NM_001352606.2:c.1274_1275del	NP_001339535.1:p.Tyr425fs	frameshift
NM_001352607.2:c.1340_1341del	NP_001339536.1:p.Tyr447fs	frameshift
NM_001352608.2:c.1196_1197del	NP_001339537.1:p.Tyr399fs	frameshift
NM_001352609.2:c.1418_1419del	NP_001339538.1:p.Tyr473fs	frameshift
NM_001352610.2:c.473_474del	NP_001339539.1:p.Tyr158fs	frameshift
NM_001352611.2:c.473_474del	NP_001339540.1:p.Tyr158fs	frameshift
NM_001352612.2:c.329_330del	NP_001339541.1:p.Tyr110fs	frameshift
NR_148027.2:n.1530_1531del		non-coding transcript variant
NR_148028.2:n.1530_1531del		non-coding transcript variant
NR_148029.2:n.1452_1453del		non-coding transcript variant
NR_148030.2:n.1530_1531del		non-coding transcript variant
NR_148031.2:n.1446_1447del		non-coding transcript variant
NC_000013.11:g.100309897_100309898del
NC_000013.10:g.100962151_100962152del
NG_008768.1:g.225815_225816del

... more HGVS ... less HGVS

Protein change

Y399fs, Y447fs, Y425fs, Y110fs, Y158fs, Y473fs

Other names

Canonical SPDI

NC_000013.11:100309895:TAT:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

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
Gene	OMIM	HI score Help 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.
PCCA		-	-	GRCh38 GRCh37	1370	1491

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.
Propionic acidemia	Pathogenic (1)	criteria provided, single submitter	Sep 30, 2023	RCV003511687.2

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.
Pathogenic (Sep 30, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Propionic acidemia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004312134.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 15464417 Comment: This sequence change creates a premature translational stop signal (p.Tyr473Cysfs8) in the PCCA gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Tyr473Cysfs8) in the PCCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCCA-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Tyr473Cysfs*8) in the PCCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCCA-related conditions. For these reasons, this variant has been classified as Pathogenic.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Propionic acidemia: mutation update and functional and structural effects of the variant alleles.	Desviat LR	Molecular genetics and metabolism	2004	PMID: 15464417

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_000282.4(PCCA):c.1418_1419del (p.Tyr473fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...