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tooluniverse-variant-interpretation

Clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis. Use for VUS classification, pathogenicity assessment with cited criteria, structure-based variant impact (AlphaFold/PDB), non-coding/regulatory variant effect prediction with sequence deep-learning models (AlphaGenome, Enformer, Borzoi, ChromBPNet, Evo 2), and producing clinical-grade variant reports for return of results or molecular tumor boards. Use this whenever a user asks about a variant's significance, an intronic/promoter/enhancer/UTR non-coding variant's functional impact, or needs ACMG classification — even if they don't say "ACMG".

Quality

89%

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SecuritybySnyk

Low

Low-risk findings worth noting

SKILL.md
Quality
Evals
Security

Quality

Content

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Reviews the quality of instructions and guidance provided to agents. Good implementation is clear, handles edge cases, and produces reliable results.

The body is a highly actionable, well-sequenced interpretation workflow with concrete tools, parameters, executable classification code, and strong error-recovery guidance. Its weaknesses are token efficiency (Phase 6 inlines the full ACMG algorithm that the referenced file is supposed to hold, plus editorial padding) and progressive disclosure (the five referenced detail files are absent from the bundle, leaving dangling pointers and an over-loaded overview).

Suggestions

Move the Bayesian point table, the classify_acmg code block, gene-specific BS1 thresholds, VCEP criteria, and predictor-weighting sections into ACMG_CLASSIFICATION.md, keeping only the point-system summary and a pointer in SKILL.md — this addresses both the conciseness and progressive-disclosure gaps.

Ship the five referenced files (ACMG_CLASSIFICATION.md, CODE_PATTERNS.md, CHECKLIST.md, EXAMPLES.md, TOOLS_REFERENCE.md) in the bundle's references/ directory — currently none exist, so every "See X" pointer (including the thresholds and code patterns the workflow depends on) is dangling.

Trim editorial commentary in Phase 6 (e.g. "This is one of the most challenging scenarios in variant interpretation", "This system handles conflicting evidence naturally") and the openended explanatory sentences around it to tighten the body without losing operational detail.

DimensionReasoningScore

Conciseness

Mostly efficient operational content (tool parameters, fallbacks, thresholds), but Phase 6 inlines a ~65-line classify_acmg function, the Bayesian point table, and gene-specific BS1 thresholds while simultaneously pointing to ACMG_CLASSIFICATION.md "for the complete algorithm", and editorial asides pad the text ("This is one of the most challenging scenarios in variant interpretation", "This system handles conflicting evidence naturally..."). Not 4: the duplication and padding exceed minor instances of over-explanation.

3 / 5

Actionability

Fully executable and copy-paste ready: the classify_acmg function runs as-is with a worked PALB2 c.2816T>G example, tools are documented with concrete parameters and return shapes (e.g. VariantValidator's genome_build/variant_description, ClinGenAllele coordinate gotcha), plus a gnomAD two-step recipe, tool-failure fallback chains, output report template, file naming convention, and quantified minimums. Matches anchor 5; not 4 because common cases are covered without gaps.

5 / 5

Workflow Clarity

Clear six-phase sequence with an overview map, conditional phases (2.5 non-coding only, 4 VUS/novel), the "LOOK UP, DON'T GUESS" gate, a Phase 2.9 short-circuit checkpoint, explicit tool-failure feedback loops (e.g. "ClinVar_search_variants returns 0 results: Use MyVariant_query_variants"), and a pre-delivery CHECKLIST.md plus quantified minimums as verification. Anchor 5 (explicit validation steps, error-recovery loops, checklist); not 4 since checkpoints are explicit rather than implicit.

5 / 5

Progressive Disclosure

References are clearly signaled and one level deep (inline "See ACMG_CLASSIFICATION.md for thresholds" pointers plus a final References section), but ~100 lines of Phase 6 detail that belong in ACMG_CLASSIFICATION.md are inlined in SKILL.md, and none of the five referenced files (ACMG_CLASSIFICATION.md, CODE_PATTERNS.md, CHECKLIST.md, EXAMPLES.md, TOOLS_REFERENCE.md) exist in the provided bundle — no references/ directory is present, so every "See X" link is dangling. Anchor 3 (content that should be separate is inline); not 4 because of the inline bulk and unverifiable references, not 2 because structure and signaling are genuinely present.

3 / 5

Total

16

/

20

Passed

Description

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Based on the skill's description, can an agent find and select it at the right time? Clear, specific descriptions lead to better discovery.

A strong description: it states concrete capabilities across the full interpretation pipeline, provides explicit when-to-use triggers with synonyms, and carves out a clear clinical niche in third-person voice. The only weakness is minor overlap risk with general sequence-analysis skills on impact-prediction phrasings.

DimensionReasoningScore

Specificity

Lists multiple specific concrete actions with comprehensive coverage: "VUS classification", "pathogenicity assessment with cited criteria", "structure-based variant impact (AlphaFold/PDB)", "non-coding/regulatory variant effect prediction with sequence deep-learning models (AlphaGenome, Enformer, Borzoi, ChromBPNet, Evo 2)", and "producing clinical-grade variant reports" span the whole pipeline from raw calls to reports. Not 4: there are no minor gaps in capability coverage.

5 / 5

Completeness

Explicitly answers both: what ("Clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis") and when ("Use for..." and "Use this whenever a user asks about a variant's significance, an intronic/promoter/enhancer/UTR non-coding variant's functional impact, or needs ACMG classification"). Matches the anchor-5 example structure exactly; not 4 because the when-clause is fully explicit with concrete trigger phrases.

5 / 5

Trigger Term Quality

Comprehensive natural-term coverage including synonyms: "a variant's significance", "intronic/promoter/enhancer/UTR non-coding variant's functional impact", "ACMG classification", plus explicit synonym handling ("even if they don't say 'ACMG'") and domain phrasings users actually say ("VUS", "molecular tumor boards", "return of results"). Not 4: no commonly used natural phrasing is missing.

5 / 5

Distinctiveness Conflict Risk

Clear niche (clinical/ACMG variant interpretation) with distinct triggers, but phrases like "a variant's... functional impact" and "structural impact analysis" could plausibly trigger a general sequence-analysis or structural-bioinformatics sibling skill (the body itself references a tooluniverse-sequence-analysis skill). Mostly distinct with minor overlap risk against closely related skills — anchor 4; not 5 because of that overlap, not 3 because the clinical/ACMG framing is strongly distinctive.

4 / 5

Total

19

/

20

Passed

Validation

100%

Checks the skill against the spec for correct structure and formatting. All validation checks must pass before discovery and implementation can be scored.

Validation — 16 / 16 Passed

Validation for skill structure

No warnings or errors.

Repository

mims-harvard/ToolUniverse

Path

plugin/skills/tooluniverse-variant-interpretation/SKILL.md

Reviewed

Table of Contents

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