MANE Collaboration

MANE Select

• One single transcript at each protein-coding locus across the genome that is representative of biology at that locus
• Useful to provide a consistent default transcript per locus across resources

MANE Plus Clinical

• Additional transcripts per locus necessary to support clinical variant reporting, e.g. which contain known pathogenic variants

Highest quality annotation

• Created jointly by Ensembl/GENCODE at EMBL-EBI, and RefSeq at NCBI
• Identified using independent computational methods complemented by manual review of key loci and discussion by expert curator scientists

Identical transcript sequences from 5' to 3'

• For each representative transcript, the pair of sequences from RefSeq and Ensembl/GENCODE are identical (5’ UTR, coding region and 3’ UTR)
• Transcript sequences retain their original identifiers / stable IDs e.g. NM_014491.4; ENST00000350908.9
• All transcript sequences perfectly match the GRCh38 reference assembly

Connect the past, present and future of clinical variant reporting

• Part of the effort to rationalise minor differences in RefSeq and Ensembl/GENCODE gene sets
• Facilitates unambiguous data exchange between specific RefSeq and Ensembl/GENCODE transcripts and the GRCh38/hg38 reference genome assembly
• Evolved to improve on previous consensus CDS (CCDS) project and LRG project (for legacy and community-requested stable sequences for reporting variants)
• Ensures compatibility with genome reference assembly-based NGS variant reporting systems

Well-supported

• Annotated in the Ensembl, NCBI and UCSC genome browsers to allow visualisation in genomic context, with all other existing annotations
• Included in other resources e.g. ClinVar and gnomAD
• Compatible with the Human Genome Variation Society (HGVS) nomenclature and supported by nomenclature checker systems (e.g. Mutalyzer, VariantValidator)
• Generated and maintained by the NCBI and EMBL-EBI