ClinVar

Description

Variant summary: SPATA7 c.3G>T (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. An alternative downstream in-frame start codon (Met 52) is located in exon 3 of the encoded protein. An activation of potential downstream translation initiation site would result in a truncated protein. At-least two other presumably pathogenic truncating variants have been reported upstream of this alternate codon in the HGMD database (example, c.20_21delTC, p.Val7Glufs*16). The variant allele was found at a frequency of 8.6e-06 in 233902 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3G>T has been reported in the literature in at-least one individual affected with Leber Congenital Amaurosis in whom a second variant was not identified (example, Perrault_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.