Finish AutoPM1

[gromdimon]

Is your feature request related to a problem? Please describe.
After #72 we have AutoPM1. We need to finish it's implementation and test it.

Describe the solution you'd like

• Implement the _get_uniprot_domain method
• Add unit tests
• Add integration tests
• Rewrite docstrings

Describe alternatives you've considered
N/A

Additional context
Some information for PM1

PM1 (hotspot)

Original Definition

Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.

-- Richards et al. (2015); Table 4

Preconditions / Precomputations

• If the variant is on chrMT then this criterion is skipped according to McCormick et al. (2020).

Implemented Criterion

• If the variant is within a hotspot (at least 4 pathogenic missense/in-frame variants within 25bp radius) then this criterion is triggered.
• If the variant is within an annotated UniProt domain and the domain contains at least 2 pathogenic variants then this criterion is triggered.

User Report

• The hotspot region definition and the number of pathogenic variants in the region.

Literature

• McCormick et al. (2020) describe the ACMG criteria for chrMT variants.

Caveats

• We currently use the threshold from PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.

Intervar

PM1 by Automated Scoring
Many protein domains play essential roles for protein function, so missense variants in these domains tend to be pathogenic. The domain information can be inferred from dbNSFP by ANNOVAR through the “dbnsfp31a_interpro” database. We first annotated all ClinVar variants (subject to the same data-cleaning procedure described above) with protein-domain information and then compiled a list in which domains contained only pathogenic or likely pathogenic variants without benign or common (allele frequency > 5%) variants. This list is provided within the InterVar package and will be updated regularly. If the user’s input variants are located in these domains, then PM1 will be applied.