Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017547.4(FOXRED1):c.-35G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
FOXRED1 (HGNC:26927): (FAD dependent oxidoreductase domain containing 1) This gene encodes a protein that contains a FAD-dependent oxidoreductase domain. The encoded protein is localized to the mitochondria and may function as a chaperone protein required for the function of mitochondrial complex I. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]
SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
c.-35 G>A in exon 1 of the FOXRED1 gene (NM_017547.3). The c.-35 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.-35 G>A variant creates an alternative ATG codon 35 base pairs upstream from the initiator Methionine codon. In the absence of RNA/functional studies, the actual effect of the c.-35 G>A sequence change is unknown. Therefore, based on the currently available information, it is unclear whether the c.-35 G>A variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). -