> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/connected-insights/interpret-and-report/inter-variant-grid/avf-introduction/avf-functional-impact-filters.md).

# 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).


---

# Agent Instructions
This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com.

## Querying This Documentation
If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question.

Perform an HTTP GET request on the current page URL with the `ask` query parameter, and the optional `goal` query parameter:

```
GET https://help.connected.illumina.com/connected-insights/interpret-and-report/inter-variant-grid/avf-introduction/avf-functional-impact-filters.md?ask=<question>&goal=<endgoal>
```

`ask` is the immediate question: it should be specific, self-contained, and written in natural language.
`goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal.

The response will contain a direct answer to the question and relevant excerpts and sources from the documentation.

Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.