Conceptual workflow of GenOtoScope.

Conceptual workflow of GenOtoScope.</p

Overview of ACMG classification tools benchmarked against GenOtoScope.

Overview of ACMG classification tools benchmarked against GenOtoScope.</p

Conceptual flowchart for examining PS1 and PM5 (PM5 Strong).

Conceptual flowchart for examining PS1 and PM5 (PM5 Strong).</p

Activation frequency ratios for MHH data set.

Log ratios calculated for each of the three classes classified by the MHH manual curators: (A) “Benign” broader class, (B) “VUS” class and (C) “Pathogenic” broader class.</p

Precision-recall curves and AUC scores of all classification tools for VCEP-HL data set.

(A) Prediction of “Benign” broader class versus “Pathogenic” broader class and “VUS” class (B) Prediction of “Pathogenic” broader class versus “Benign” broader class and “VUS” class (C) Prediction of “VUS” class versus “Benign” broader class and “Pathogenic” broader class.</p

ROC curves and AUC scores of all classification tools for VCEP-HL data set.

(A) Prediction of “Benign” broader class versus “Pathogenic” broader class and “VUS” class (B) Prediction of “Pathogenic” broader class versus “Benign” broader class and “VUS” class (C) Prediction “VUS” class versus “Benign” broader class and “Pathogenic” broader class.</p

Web interface of GenOtoScope.

(A) The home page of the GenOtoScope website. (B) The resulted variant classification page, for an example variant (RS id: 1064797096), which includes its classification based on HL-specified ACMG guidelines.</p

Precision-recall curves and AUC scores of all classification tools for the MHH data set.

(A) Prediction of “Benign” broader class versus “Pathogenic” broader class and “VUS” class (B) Prediction of “Pathogenic” broader class versus “Benign” broader class and “VUS” class (C) Prediction of “VUS” class versus “Benign” broader class and “Pathogenic” broader class.</p

Overview of ACMG/AMP evidence-based criteria.

Green marks show implemented criteria. Grey font shows not implemented criteria. Striked-through shows removed or not applicable criterion for hearing loss. Thresholds shown for BA1 and BS1 are specific for HL.</p

Conceptual workflow to call critical regions of proteins for assessment of PVS1 rule.

(TIF)</p