splice site variant
A genetic alteration affecting RNA splicing signals that can disrupt normal mRNA processing, potentially leading to aberrant protein products or nonsense-mediated decay.
Full Definition
A splice site variant is a genetic alteration that affects the DNA sequences required for proper RNA splicing, including donor sites (GT), acceptor sites (AG), and branch points. These variants can cause exon skipping, intron retention, or activation of cryptic splice sites, resulting in aberrant mRNA transcripts. Splice site variants are classified based on their location and predicted impact: those affecting canonical splice sites (±1, ±2 positions) are typically considered pathogenic, while variants in more distant positions require functional assessment. In cancer genetics, splice site variants in tumor suppressor genes like BRCA1, BRCA2, or TP53 are often loss-of-function alterations. Prediction tools and RNA studies may be needed to determine the functional consequences of novel splice site variants.
Usage
Usage note: Hyphenate when used as compound modifier; specify position relative to exon-intron boundary when possible.
In Context
- "The splice site variant resulted in exon 7 skipping and premature protein truncation." — Functional analysis report
- "A canonical splice site variant at the +1 position was predicted to abolish normal splicing." — Variant interpretation summary