Q. Why is Cryptic Native Frequency (NIF) displayed for Donor variants but not for Acceptor variants?

A. The successful recognition of an acceptor motif relies on key auxiliary factors, namely branch-point and poly pyrimidine tract. The acceptor motif's Native Frequency (NIF) alone does not capture these two auxiliary factors. This is currently an area of research and it is not possible to accurately reflect the acceptor splice-site strength based on the acceptor motif's NIF alone. As a result, we have removed the Cryptic NIF column for acceptor variants for now. This will be reintroduced once we have a metric that accurately captures the acceptor strength along with its auxiliary factors.

Disrupts Splicing

Clinical and genetic evidence indicate this variant is likely to disrupt pre-mRNA splicing for this gene.

Maintains Splicing

Clinical and genetic evidence indicate this variant is likely to maintain the existing pattern of pre-mRNA splicing for this gene.

Uncertain

Clinical and genetic evidence for pre-mRNA splicing disruption by this variant is weak and/or conflicting; and a splicing outcome cannot be determined.