ClinVar

This variant is classified as a variant of unknown significance because its contribution to the phenotype of Joubert syndrome (JBTS17; 614615) has not been confirmed.

In 4 patients from 3 unrelated French Canadian families with Joubert syndrome, Srour et al. (2012) identified a heterozygous 4690G-A transition in exon 40a of the C5ORF42 gene, resulting in an ala1564-to-thr (A1564T) substitution. Each patient carried another pathogenic mutation in the C5ORF42 gene on the other allele (see, e.g., 614571.0001). The A1564T substitution was not found in 261 control exomes, in the 1000 Genomes Project database, or in 477 French Canadian controls. However, it was found in heterozygous state in the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project database, with a minor allele frequency of 0.262% (12 of 4,574 alleles). This variant has been designated rs111294855. It was not possible to predict the effect of the A1564T substitution because the corresponding exon was not annotated across species, and Srour et al. (2012) noted that it is possible that this variant may be linked to another pathogenic mutation.