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 SCN2ABRCA1 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.
TRANSCRIPT QC
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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.
| status | meaning | suggested check |
|---|---|---|
MANE_SELECT |
matches the current MANE Select | none |
MANE_PLUS_CLINICAL |
a MANE Plus Clinical isoform | state why this isoform is used |
OLD_VERSION |
right transcript, outdated version | update version, re-validate the c. position |
MANE_SELECT_CHANGED |
used to be MANE Select; the selection moved to another accession (from MANE's own change list, with CDS affected: yes/no) | move to the current MANE Select, re-map |
NON_MANE |
not a MANE transcript for the gene | review against MANE Select / Plus Clinical; document the rationale if retained |
GENE_MISMATCH |
the accession is MANE for a different gene | fix gene or transcript |
GENE_NOT_IN_MANE |
protein-coding gene without a MANE transcript yet | follow gene-specific or laboratory transcript-selection policy |
NEWER_VERSION |
newer than the snapshot | refresh the snapshot (--mane current) |
UNKNOWN_TRANSCRIPT / UNKNOWN_GENE / UNPARSEABLE |
cannot resolve | add gene · check symbol · fix accession |
Genes with a Plus Clinical isoform are flagged on every row of that gene: check which isoform actually carries the variant.
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.
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)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.
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.
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.
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.
Soloshenko M. transcriptQC (manecheck): MANE Select / MANE Plus Clinical transcript check against the MANE reference set. 2026. doi:10.5281/zenodo.22285580 (concept DOI, all versions; v0.1.1 = 10.5281/zenodo.22285581). Machine-readable in CITATION.cff.
MIT — Margarita Soloshenko, 2026. MANE data © NCBI/EMBL-EBI, public domain / open licence per their terms.