Skip to main content
scientific-variant-interpretation 遺伝子バリアント臨床解釈スキル。ClinVar / gnomAD / COSMIC / ACMG ガイドラインに
基づく病原性評価、薬理ゲノミクス（PharmGKB/ClinPGx）、バリアント-表現型相関の
エビデンスグレーディング。ToolUniverse の Variant Interpretation パラダイムを統合。
「バリアントの病原性を評価して」「pharmacogenomics 解析して」で発火。
Ir para a instalação Skills Marketplace Descubra e explore skills de IA criadas pela comunidade.
Instalar com Codex ou Claude Copie este prompt, cole no Codex, Claude ou outro assistente e deixe que ele revise a página da skill e instale para você.
Mostrar detalhes do prompt Um comando direto ignora o prompt de revisão. Verifique a origem antes de executá-lo.
npx skills add https://github.com/nahisaho/satori --skill scientific-variant-interpretationO comando permanece em uma só linha. Role horizontalmente para revisá-lo antes de copiar.
Prefere uma cópia local? Baixe os arquivos disponíveis atualmente no SkillsMP.
Baixar Zip Baixando... Ocupações relacionadas SOC
Baseado na classificação ocupacional SOC
name scientific-variant-interpretation description 遺伝子バリアント臨床解釈スキル。ClinVar / gnomAD / COSMIC / ACMG ガイドラインに
基づく病原性評価、薬理ゲノミクス（PharmGKB/ClinPGx）、バリアント-表現型相関の
エビデンスグレーディング。ToolUniverse の Variant Interpretation パラダイムを統合。
「バリアントの病原性を評価して」「pharmacogenomics 解析して」で発火。
tu_tools [{"key":"clinvar","name":"ClinVar","description":"臨床的バリアント解釈データベース"}]
Scientific Variant Interpretation
遺伝子バリアントの臨床的解釈スキル。ACMG/AMP ガイドラインに準拠した
病原性分類、薬理ゲノミクスによる薬物応答予測、体細胞変異の
ドライバー/パッセンジャー判定を統合的に実行する。
When to Use
SNV/Indel の病原性を ACMG 基準で分類するとき
薬理ゲノミクス (PGx) による薬物応答予測を行うとき
がん体細胞変異のドライバー判定を行うとき
希少疾患の原因バリアント同定を支援するとき
バリアント-表現型相関のエビデンスを評価するとき
Quick Start
バリアント解釈パイプライン
Input: Variant (HGVS notation / rsID / genomic coordinates)
↓
Step 1: Annotation
- ClinVar 臨床意義
- gnomAD 集団頻度
- InterVar ACMG 自動分類
↓
Step 2: Population Frequency
- gnomAD allele frequency
- 民族・集団別頻度
- 稀少性判定 (AF < 0.01 or 0.001)
↓
Step 3: Functional Impact
- CADD / REVEL / AlphaMissense スコア
- 保存度 (PhyloP, GERP++)
- スプライス予測 (SpliceAI)
↓
Step 4: Clinical Evidence
- ClinVar submissions
- COSMIC (体細胞変異)
- Literature evidence (PubMed)
↓
Step 5: ACMG Classification
- 28 基準の系統的適用
- 5 段階分類 (P, LP, VUS, LB, B)
↓
Output: Variant Interpretation Report
Phase 1: ACMG/AMP 分類
28 基準の系統的評価
ACMG_CRITERIA = {
"PVS1" : "Null variant (nonsense, frameshift, canonical splice) in LOF-intolerant gene" ,
"PS1"
"Same amino acid change as established pathogenic variant"
"PS2"
"De novo (confirmed parentage) in patient with disease"
"PS3"
"Functional study shows damaging effect"
"PS4"
"Prevalence in affected >> controls (OR > 5)"
"PM1"
"In mutational hot spot or critical functional domain"
"PM2"
"Absent from controls (or extremely rare in gnomAD)"
"PM3"
"Detected in trans with pathogenic variant (recessive)"
"PM4"
"Protein length change (in-frame del/ins in non-repeat region)"
"PM5"
"Novel missense at same position as established pathogenic"
"PM6"
"Assumed de novo (parentage not confirmed)"
"PP1"
"Co-segregation with disease in multiple family members"
"PP2"
"Missense in gene with low rate of benign missense"
"PP3"
"Computational evidence supports deleterious effect"
"PP4"
"Patient phenotype highly specific for gene"
"PP5"
"Reputable source reports as pathogenic"
"BA1"
"Allele frequency > 5% in any population"
"BS1"
"Allele frequency greater than expected for disorder"
"BS2"
"Observed in healthy adult (for early-onset/penetrant disorder)"
"BS3"
"Functional study shows no damaging effect"
"BS4"
"Lack of segregation in affected family members"
"BP1"
"Missense in gene where only truncating cause disease"
"BP2"
"Observed in trans with pathogenic variant (dominant)"
"BP3"
"In-frame del/ins in repetitive region"
"BP4"
"Computational evidence suggests no impact"
"BP5"
"Variant found in case with alternate molecular basis"
"BP6"
"Reputable source reports as benign"
"BP7"
"Synonymous with no splicing impact predicted"
def
classify_acmg
criteria_met
"""
適用された ACMG 基準から最終分類を導出。
Richards et al., Genetics in Medicine 2015
"""
for
in
if
"PVS"
"PS"
"PM"
"PP"
for
in
if
"BA"
"BS"
"BP"
for
in
if
"PVS"
for
in
if
"PS"
for
in
if
"PM"
for
in
if
"PP"
for
in
if
"BA"
for
in
if
"BS"
for
in
if
"BP"
if
len
1
and
len
1
or
len
2
or
len
1
and
len
1
or
len
2
return
"Pathogenic"
if
len
2
return
"Pathogenic"
if
len
1
and
len
1
return
"Likely Pathogenic"
if
len
1
and
len
1
or
len
2
return
"Likely Pathogenic"
if
len
1
return
"Benign"
if
len
2
return
"Benign"
if
len
1
and
len
1
return
"Likely Benign"
if
len
2
return
"Likely Benign"
return
"Variant of Uncertain Significance (VUS)"
Phase 2: 薬理ゲノミクス (PGx)
PharmGKB / CPIC ガイドライン PGX_GENES = {
"CYP2D6" : {
"drugs" : ["codeine" , "tramadol" , "tamoxifen" , "atomoxetine" ],
"phenotypes" : ["Poor Metabolizer" , "Intermediate" , "Normal" , "Ultrarapid" ],
},
"CYP2C19" : {
"drugs" : ["clopidogrel" , "voriconazole" , "escitalopram" , "omeprazole" ],
"phenotypes" : ["Poor Metabolizer" , "Intermediate" , "Normal" , "Rapid" , "Ultrarapid" ],
},
"CYP2C9" : {
"drugs" : ["warfarin" , "phenytoin" , "celecoxib" ],
"phenotypes" : ["Poor Metabolizer" , "Intermediate" , "Normal" ],
},
"DPYD" : {
"drugs" : ["fluorouracil" , "capecitabine" ],
"phenotypes" : ["Poor Metabolizer" , "Intermediate" , "Normal" ],
},
"TPMT" : {
"drugs" : ["azathioprine" , "mercaptopurine" , "thioguanine" ],
"phenotypes" : ["Poor Metabolizer" , "Intermediate" , "Normal" ],
},
"HLA-B" : {
"variants" : {"*57:01" : "abacavir hypersensitivity" , "*58:01" : "allopurinol SJS/TEN" },
},
}
def pgx_recommendation (gene, phenotype, drug ):
"""
CPIC ガイドラインに基づく薬物用量推奨。
"""
recommendations = {
"avoid" : "代替薬の使用を推奨" ,
"reduce_dose" : "標準用量の 25-50% に減量" ,
"standard_dose" : "標準用量で開始" ,
"increase_dose" : "標準用量で効果不十分の可能性、増量を検討" ,
}
return recommendations
Phase 3: 体細胞変異解釈
OncoKB / COSMIC エビデンスレベル ## Somatic Variant Interpretation
### Oncogenicity Classification
| Level | Description |
|-------|-------------|
| Oncogenic | Functionally validated driver |
| Likely Oncogenic | Strong computational/indirect evidence |
| VUS | Insufficient evidence |
| Likely Benign | Evidence against oncogenicity |
| Benign | Confirmed passenger |
### Therapeutic Actionability (OncoKB Levels)
| Level | Description |
|-------|-------------|
| 1 | FDA-approved, same tumor type |
| 2 | Standard care, different tumor type |
| 3A | Clinical evidence in same tumor type |
| 3B | Clinical evidence in different tumor type |
| 4 | Preclinical evidence |
| R1 | Resistance to approved therapy |
| R2 | Resistance to investigational therapy |
Report Template # Variant Interpretation Report
**Variant** : [HGVS notation]
**Gene** : [gene symbol]
**Date** : [date]
## 1. Variant Summary
| Feature | Value |
|---------|-------|
| Genomic location | |
| Transcript | |
| Protein change | |
| Variant type | |
## 2. Population Frequency
| Database | Frequency | Population |
|----------|-----------|------------|
## 3. In Silico Predictions
| Tool | Score | Prediction |
|------|-------|------------|
| CADD | | |
| REVEL | | |
| AlphaMissense | | |
| SpliceAI | | |
## 4. Clinical Evidence
### 4.1 ClinVar
### 4.2 Literature
### 4.3 Functional Studies
## 5. ACMG Classification
| Criterion | Applied | Evidence |
|-----------|---------|----------|
**Final Classification** : [P/LP/VUS/LB/B]
## 6. Pharmacogenomic Implications
（該当する場合）
## 7. Treatment Implications
（がん体細胞変異の場合）
## 8. Recommendations
Completeness Checklist
Best Practices
ACMG は系統的に : 全 28 基準を 1 つずつ評価し、根拠を明記集団頻度はサブ集団で確認 : 特定民族でのみ高頻度な場合がある機能研究を重視 : 計算予測よりも実験的エビデンスが優先ClinVar は星評価を確認 : 3-4 星のエントリが最も信頼性が高いPGx は CPIC レベルを確認 : Level A/B のみ臨床実装
References
Output Files ファイル 形式 生成タイミング results/variant_report.mdバリアント解釈レポート（Markdown） 全解析完了時 results/variant_classification.jsonACMG/AMP 分類データ（JSON） 分類完了時 results/pgx_report.json薬理ゲノミクスレポート（JSON） PGx 評価完了時
利用可能ツール カテゴリ 主要ツール 用途 ClinVar clinvar_search_variantsバリアントの病原性分類検索 gnomAD gnomad_get_gene_constraints遺伝子制約メトリクス（pLI / LOEUF） ClinGen ClinGen_get_gene_validity遺伝子-疾患の妥当性評価 AlphaMissense AlphaMissense_get_variant_scoreミスセンス病原性予測スコア PharmGKB PharmGKB_search_variants薬理ゲノミクスバリアント検索 CADD CADD_get_variant_scoreバリアント有害性スコア MyVariant MyVariant_get_variant_annotation統合バリアントアノテーション
参照スキル スキル 連携 scientific-bioinformatics← ゲノムデータ・バリアントコール scientific-sequence-analysis← 配列コンテキスト・保存度情報 scientific-data-preprocessing← バリアントデータの前処理・正規化 scientific-clinical-decision-support→ バリアント解釈結果の臨床意思決定 scientific-academic-writing→ 研究成果の論文化 scientific-pharmacogenomics← Star アレル・代謝型・薬理ゲノミクス
