Submissions for variant NM_144997.7(FLCN):c.1176+3G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003044892	SCV003350682	uncertain significance	Birt-Hogg-Dube syndrome	2022-05-05	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). 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. 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 is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This sequence change falls in intron 10 of the FLCN gene. It does not directly change the encoded amino acid sequence of the FLCN protein. It affects a nucleotide within the consensus splice site.
Ambry Genetics	RCV004948942	SCV005581701	uncertain significance	Hereditary cancer-predisposing syndrome	2024-09-25	criteria provided, single submitter	clinical testing	The c.1176+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 7 in the FLCN gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear.