# Functional Impact Filters

This page summarizes filters related to the functional impact of a variant. Filter availability can vary depending on the selected variant categories. If filters are applied to more than one variant category in the same condition group, only filters relevant for all variant categories are available. For more information,refer to [Filter by Variant Category](/connected-insights/interpret-and-report/inter-variant-grid/avf-introduction/avf-filter-by-variant-category.md).

## Constraint Metrics (gnomAD)

Filters by gnomAD constraint metrics: LOEUF, misZ, pLI, misZ, pLI, pNull, pRec, and synZ. For more information, refer to [Acronyms and Terms](/connected-insights/resources-and-references/rar-acronyms-and-terms.md).

## Haploinsufficiency and Triplosensitivity (ClinGen)

Filters by the haploinsufficiency and triplosensitivity evidence classification. It represents the strength of evidence supporting a relationship between a gene and disease and whether loss (haploinsufficiency) or gain (triplosensitivity) of individual genes or genomic regions is a mechanism for disease(Riggs et al., Clin Genet. 81, 403–412 (2012)).

The evidence categories can be used for clinical interpretation of copy number variants using the categories recommended by ClinGen.

### Evidence Classification

| **Evidence Classification**   | **Haploinsufficiency and TriplosensitivityScore** | **Suggested Classification** |
| ----------------------------- | ------------------------------------------------- | ---------------------------- |
| Sufficient Evidence           | 3                                                 | Pathogenic                   |
| Emerging Evidence             | 2                                                 | Likely Pathogenic            |
| Little Evidence               | 1                                                 | VUS                          |
| No Evidence                   | 0                                                 | VUS                          |
| Sensitivity Unlikely          | 40: Dosage Sensitivity Unlikely                   | Likely Benign/Benign         |
| Autosomal Recessive Phenotype | 30: Autosomal Recessive                           | Not applicable               |

## SpliceAI

Filters by the SpliceAI score. For more information, refer to [Acronyms and Terms](/connected-insights/resources-and-references/rar-acronyms-and-terms.md).

## PrimateAI-3D

Filters by the PrimateAI-3D score. For more information, refer to [Acronyms and Terms](/connected-insights/resources-and-references/rar-acronyms-and-terms.md).


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