ClinVar

Description

Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 6 (i.e. the last exon) in the TMEM38B gene. A presumed nomenclature of c.(660+1_661-1)_(*2532_?)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a large truncation of the encoded protein (removing amino acids 220-291), and likely replacing it with an incorrect sequence. A large deletion variant (size: 195,085 bp; position: chr9:108535399-108730484), which extends ~191 kbp beyond the TMEM38B gene, but it doesn't affect other genes, was found at a frequency of 0.00018 in 21694 control chromosomes (i.e. in 4 heterozygous carriers) in the gnomAD database, structural variants dataset. To our knowledge, no occurrence of c.(660+1_661-1)_(*2532_?)del in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.