We observed 428 recurrent and 328 nonrecurrent synonymous variants in the X-specific part of the X chromosome. Although most synonymous variants are biologically silent, a small subset may exert cryptic biological effects through alterations in transcript processing or splicing. To search for additional cryptic splice variants, we applied the program NNsplice27 to all synonymous and missense base substitutions. Three synonymous and seven missense variants were predicted with a high score (>0.9) to introduce a new splice site (Supplementary Table 6 online). One of these is the missense variant in CASK (described above) that causes an abnormality of splicing. Of the remainder, five were recurrent and four were nonrecurrent variants. As all the likely mental retardation–causing variants thus far discovered in this study are nonrecurrent, these results suggest that many of the variants predicted to alter splicing are not implicated in mental retardation.
