rs267608668

Description

The POLR3A c.1674C>G (p.Phe558Leu) missense variant has been reported in two studies in which it is found in a compound heterozygous state in two individuals, one individual with early onset tremor-ataxia with central hypomyelination in whom the p.Phe558Leu variant was in trans with an inframe insertion, and one individual with 4H leukodystrophy in whom the p.Phe558Leu variant was in trans with a missense variant (Bernard et al. 2011; Wolf et al. 2014). The p.Phe558Leu variant was absent from 250 control chromosomes and is not found in 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Consortium. The evidence for this variant is limited. The p.Phe558Leu variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for pol III-related leukodystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.