transcriptQC · manecheck

Is this transcript aligned with the current MANE reference set? Variant reports arrive on old or arbitrary RefSeq/Ensembl transcripts: NM_007294.3, NM_021007.2, ENST…. MANE is the NCBI/EMBL-EBI reference set for exactly this — MANE Select is one agreed transcript per gene, MANE Plus Clinical adds isoforms needed for known clinically relevant variants. manecheck compares what you were given with a versioned MANE snapshot and reports the alignment with a suggested action, one transcript or a whole lab table at a time, offline, from the MANE bulk files shipped inside the package. It is a reference-choice QC, not a transcript-selection policy: a non-MANE transcript can be the right choice with a documented rationale.

pip install transcriptqc
manecheck variants.csv --html report.html          # columns: gene, transcript, variant (any subset; or one HGVS column)
manecheck "NM_007294.3:c.5266dupC"
manecheck NM_021007.2 --gene SCN2A
manecheck SCN2A

What it says

BRCA1  c.5266dupC
  Input transcript:      NM_007294.3
  Current MANE Select:   NM_007294.4
  Status:                OLD_VERSION ⚠
  Action:                update transcript version; re-validate c. position
  Note:                  current version is NM_007294.4

SCN2A  c.4766A>G
  Input transcript:      NM_021007.2
  Current MANE Select:   NM_001040142.2
  MANE Plus Clinical:    NM_001371246.1
  Status:                NON_MANE ⚠
  Action:                re-report on the MANE Select (or justify)
  Note:                  gene has MANE Plus Clinical transcript(s): NM_001371246.1 — check which isoform carries the variant

BRCA1  c.100A>G
  Input transcript:      NM_000059.4
  Current MANE Select:   NM_007294.4
  Status:                GENE_MISMATCH ✗
  Action:                fix gene or transcript
  Note:                  NM_000059.4 is the MANE Select transcript of BRCA2, not BRCA1

Note the second one: the report in the brief assumed SCN2A's MANE Select was NM_021007.x. In MANE v1.5 it is NM_001040142.2, and there is a Plus Clinical isoform NM_001371246.1 — exactly the kind of thing this tool is for. The third catches a transcript pasted from the wrong gene.

The batch summary

TRANSCRIPT QC
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
14 transcripts checked · MANE v1.5 (bundled)

✗    1 gene mismatch
✗    1 unparseable
⚠    1 mane select changed
⚠    3 old version
⚠    2 non mane
?    1 unknown gene
✓    5 mane select
ℹ    1 genes with a relevant MANE Plus Clinical transcript

Potential reporting problems: 9

--csv, --json and --html write the table (see examples/report.html); --fail exits 1 when any potential problem is present, so it can gate a pipeline or a report sign-off.

Statuses

Genes with a Plus Clinical isoform are flagged on every row of that gene: check which isoform actually carries the variant.

Reproducible by construction

The package bundles MANE v1.5 (summary, changed_select_accessions, protein_coding_genes_not_in_mane from the NCBI bulk directory). Every report states the release it was checked against. --mane 1.6 or --mane current downloads another release once into ~/.cache/transcriptqc; nothing else touches the network. RefSeq (NM_/NR_/XM_/XR_) and Ensembl (ENST) accessions both work, with or without version.

Python API

from transcriptqc import load_mane, check_transcript, check_hgvs, check_file, mane_for_gene
m = load_mane()                                   # bundled v1.5
check_transcript("NM_007294.3", gene="BRCA1", mane=m).status     # 'OLD_VERSION'
check_hgvs("NM_007294.3:c.5266dupC", m).mane_select              # 'NM_007294.4'
mane_for_gene("SCN2A", m)["plus_clinical"]
results = check_file("variants.csv", m)

Tests

Six offline tests on the bundled snapshot: real MANE values (BRCA1, SCN2A with its Plus Clinical isoform), every status with the case that triggers it, the change list (ACHE moved to NM_000665.5, ACYP2's change affects the CDS), a gene not in MANE (AKR7L), HGVS forms, file input with mixed columns, and all four report formats. 84 % line coverage.

Not in scope, on purpose

It checks the transcript, not the variant: no HGVS validation, no coordinate lift between versions (use VariantValidator or Mutalyzer for that; this tells you when you need to). MANE transcript definitions are anchored to GRCh38; this tool does not validate assembly-specific genomic coordinates. MANE mappings to GRCh37 and other assemblies are provided separately by NCBI and are not used here.

Roadmap

assembly check when genomic coordinates are supplied · Ensembl ↔ RefSeq consistency check on paired accessions · MANE version diff (manecheck diff 1.4 1.5) · VCF INFO field check · pairs with VariantStory and vus-recheck.

Name

Repository transcriptQC, command manecheck (also transcriptqc): MANE is the engine today; version freshness, RefSeq/Ensembl matching and assembly checks fit under the wider name later without renaming. An unrelated eastgenomics/ManeCheck repository exists on GitHub.

Cite

Solosenko M. transcriptQC: MANE Select / MANE Plus Clinical transcript check for clinical reporting. 2026. doi:10.5281/zenodo.22285580 (concept DOI, all versions; v0.1.1 = 10.5281/zenodo.22285581). Machine-readable in CITATION.cff.

License

MIT — Margarita Solosenko, 2026. MANE data © NCBI/EMBL-EBI, public domain / open licence per their terms.