Submissions for variant NM_000064.4(C3):c.1269+4C>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294710	SCV002587668	uncertain significance	Atypical hemolytic-uremic syndrome	2020-04-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003542351	SCV004247488	uncertain significance	not provided	2023-01-27	criteria provided, single submitter	clinical testing	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. ClinVar contains an entry for this variant (Variation ID: 1712455). This variant has not been reported in the literature in individuals affected with C3-related conditions. This variant is present in population databases (rs545213448, gnomAD 0.01%). This sequence change falls in intron 11 of the C3 gene. It does not directly change the encoded amino acid sequence of the C3 protein. It affects a nucleotide within 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.