Submissions for variant NM_000064.4(C3):c.3490-10T>G

gnomAD frequency: 0.00053  dbSNP: rs372843505

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002104929	SCV002383371	likely benign	not provided	2025-01-06	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV002104929	SCV002501497	uncertain significance	not provided	2021-06-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331293	SCV004038784	likely benign	not specified	2023-08-22	criteria provided, single submitter	clinical testing	Variant summary: C3 c.3490-10T>G alters a non-conserved nucleotide located at a position not widely known to affect splicing. 3/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0001 in 251410 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3490-10T>G in individuals affected with C3 Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.