Submissions for variant NM_000282.4(PCCA):c.1209+3A>G

dbSNP: rs1467680142

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668869	SCV000793542	likely pathogenic	Propionic acidemia	2017-08-18	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000668869	SCV001441003	pathogenic	Propionic acidemia	2019-01-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002275128	SCV002563176	likely pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000668869	SCV004296514	pathogenic	Propionic acidemia	2022-11-07	criteria provided, single submitter	clinical testing	This sequence change falls in intron 13 of the PCCA gene. It does not directly change the encoded amino acid sequence of the PCCA protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PCCA protein in which other variant(s) (p.Arg399Trp) have been determined to be pathogenic (PMID: 30274917; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 13, but is expected to preserve the integrity of the reading-frame (PMID: 17051315, 21094621). ClinVar contains an entry for this variant (Variation ID: 553422). This variant has been observed in individuals with propionic acidemia (PMID: 17051315, 22033733, 31319225). This variant is present in population databases (no rsID available, gnomAD 0.0009%).