ClinVar

Description

Variant summary: CFTR c.3038C>T (p.Pro1013Leu) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251514 control chromosomes (gnomAD and publication data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3038C>T has been reported in the literature in individuals affected with Cystic Fibrosis (Onay_1998, Kilinc_2002, Elahi_2006, Schippa_2013, Castaldo_2020, Erdoan_2021). These reports do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Hammerle_2001). The following publications have been ascertained in the context of this evaluation (PMID: 12007216, 33572515, 32784480, 11504857, 16436643, 34860163, 11278813, 34426522, 12439892, 25880441, 25910067, 17594398, 9521595, 25735457, 34996830, 23613805, 26437683). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.