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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".

71

Quality

86%

Does it follow best practices?

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SecuritybySnyk

Low

Low-risk findings worth noting

The canonical home for this skill is tooluniverse-variant-interpretation in mims-harvard/ToolUniverse

SKILL.md
Quality
Evals
Security

Quality

Content

81%Weight 40%Scale 1-5

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

A highly actionable, well-sequenced clinical workflow with concrete tools, code, fallbacks, and verification minimums throughout. Its weaknesses are token bloat from inlining material that duplicates its own referenced files, and a reference structure whose target files are not verifiable in the bundle.

Suggestions

Move the full Bayesian point table and classify_acmg function into ACMG_CLASSIFICATION.md and keep only the classification thresholds and a pointer inline, since the body already says 'See ACMG_CLASSIFICATION.md for thresholds'.

Trim per-tool parameter/return documentation (Phase 1, Phase 4) down to one-line usage notes and defer detail to TOOLS_REFERENCE.md.

Condense the 'Handling Conflicting Evidence' section to its decision rules and ship the referenced bundle files (ACMG_CLASSIFICATION.md, CODE_PATTERNS.md, CHECKLIST.md, EXAMPLES.md, TOOLS_REFERENCE.md) alongside SKILL.md so the references resolve.

DimensionReasoningScore

Conciseness

The body is dense with genuinely non-obvious operational knowledge (gnomAD two-step workflow, tool fallbacks, env-var requirements, AlphaFold size limits), but it is padded by a ~60-line inline classify_acmg function with docstring and example, per-tool parameter/return documentation that duplicates the referenced TOOLS_REFERENCE.md, and a four-point essay on conflicting evidence. It fits the 'mostly efficient but could be tightened' anchor better than the verbose 2 anchor because most content is skill-specific rather than concepts Claude already knows.

3 / 5

Actionability

Guidance is fully executable: a copy-paste-ready classify_acmg Python function, a concrete ESM_explain_variant_mechanism call with parameter annotations, named tools with parameters and return shapes, explicit fallback chains per failure mode, a report output template, file naming convention, and quantified minimums. This matches the 'fully executable, copy-paste ready' anchor.

5 / 5

Workflow Clarity

Phases 1 through 6 are clearly sequenced with an overview diagram, a short-circuit check (Phase 2.9), per-tool failure fallbacks that function as error-recovery feedback loops, and verification via the quantified-minimums table and CHECKLIST.md pre-delivery checklist. This matches the top anchor's 'explicit validation steps; feedback loops; checklists for complex processes'.

5 / 5

Progressive Disclosure

The References section lists five one-level-deep files with descriptive annotations and inline pointers ("See ACMG_CLASSIFICATION.md for thresholds"), which is good structure. It falls short of 5 because substantial content that belongs in those referenced files is inlined anyway (the full Bayesian point table plus the classify_acmg function despite ACMG_CLASSIFICATION.md existing; parameter blocks despite TOOLS_REFERENCE.md), and none of the referenced bundle files are actually present to verify.

4 / 5

Total

17

/

20

Passed

Description

92%Weight 40%Scale 1-5

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 that explicitly states both what the skill does and when to use it, with concrete capabilities and thoughtful trigger phrasing ("even if they don't say 'ACMG'"). The only weakness is a handful of missing natural trigger terms such as VCF, variant annotation, and the database names users commonly mention.

Suggestions

Add high-frequency natural trigger terms like "VCF", "variant annotation", and "ClinVar/gnomAD lookup" to the 'Use this whenever' clause.

Trim the enumerated model list (AlphaGenome, Enformer, Borzoi, ChromBPNet, Evo 2) to one or two exemplars plus a category phrase to reduce length without losing triggers.

DimensionReasoningScore

Specificity

The description lists multiple concrete actions — "VUS classification, pathogenicity assessment with cited criteria, structure-based variant impact (AlphaFold/PDB), non-coding/regulatory variant effect prediction with sequence deep-learning models... producing clinical-grade variant reports" — with comprehensive coverage of the skill's capabilities. It exceeds the 4 anchor because there are no notable gaps in action coverage.

5 / 5

Completeness

It explicitly answers both questions: what ("Clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis") and when ("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"). This matches the 5 anchor with concrete trigger phrases.

5 / 5

Trigger Term Quality

Good keyword coverage including natural phrases like "a variant's significance", "VUS", "pathogenicity", "intronic/promoter/enhancer/UTR", and "ACMG classification — even if they don't say ACMG". A few natural terms users would say are missing, such as "VCF", "variant annotation", or database names (ClinVar, gnomAD), so it sits between the 4 and 5 anchors rather than clearly at 5.

4 / 5

Distinctiveness Conflict Risk

It occupies a clear clinical-variant-interpretation niche with distinct triggers (ACMG classification, VUS, non-coding regulatory impact, molecular tumor boards), minimizing conflict risk with unrelated skills. It is not merely "mostly distinct" as the 4 anchor describes.

5 / 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
Reviewed

Table of Contents

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