A joint NCBI and EMBL-EBI transcript set for clinical genomics and research

Area of Science:

• Genomics
• Bioinformatics
• Clinical Genetics

Background:

• Genome annotation is crucial for understanding clinically relevant variants.
• Lack of standardized clinical reporting and browser display hinders consistent interpretation.
• The Ensembl/GENCODE and RefSeq databases have collaborated to address these challenges.

Purpose of the Study:

• To describe the Matched Annotation from NCBI and EMBL-EBI (MANE) transcript sets.
• To establish universal standards for variant reporting and genome browser display.
• To improve consistency and streamline clinical interpretation of genetic variants.

Main Methods:

• The MANE collaboration converged Ensembl/GENCODE and RefSeq human gene and transcript annotation.
• Defined a high-value set of transcripts and corresponding proteins.
• Created MANE Select and MANE Plus Clinical transcript sets.

Main Results:

• Released MANE Select transcripts for 97% of human protein-coding genes, including ACMG Secondary Findings genes.
• MANE transcripts ensure exact matches between Ensembl/GENCODE and RefSeq exonic sequences.
• MANE transcripts are accessible via major genome browsers and key resources.

Conclusions:

• MANE transcript sets provide a universal standard for variant reporting and genome browser display.
• Widespread adoption will enhance reporting consistency and data exchange.
• MANE facilitates streamlined clinical interpretation of genetic variants.