> 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/emedgene/emedgene-analyze-manual/variant_page/clinical_significance_section/gene-metrics.md).

# Gene metrics

The Gene metrics card helps you assess whether a gene is tolerant or intolerant to variation. It includes:

* **Intolerance metrics** from ExAC and gnomAD that relate to gene constraint and variant burden
* **Direct links** to ExAC and gnomAD for quick access
* **Resources field (v100.39.0+)** with links to external gene databases offering detailed information on gene function and clinical relevance:
  * ClinGen gene
  * DECIPHER gene
  * GenCC
  * OMIM gene

## Metrics and interpretation

{% tabs %}
{% tab title="p(LoF intolerant)" %}
pLI = p(LoF intolerant) is a probability of being loss-of-function intolerant to heterozygous and homozygous LoF variants.

Scale:

* 🔴 pLI ≥ 0.9: extremely LoF intolerant,
* 🟠 pLI > 0.1 & < 0.9: intermediate value,
* 🟢 pLI ≤ 0.1: LoF tolerant.
  {% endtab %}

{% tab title="Missense Z-score" %}
The missense Z-score indicates intolerance to missense variants based on the deviation of observed missense variants versus the expected number.

Scale:

* 🔴 Missense Z ≥ 3: missense intolerant,
* 🟠 Missense Z > 2.5 & < 3: intermediate value,
* 🟢 Missense Z ≤ 2.5: missense tolerant.
  {% endtab %}

{% tab title="p(REC)" %}
p(REC) is a probability of being intolerant to homozygous, but not heterozygous LoF.

Scale:

* 🔴 p(REC) ≥ 0.8: Hom LoF intolerant,
* 🟠 p(REC) > 0.2 & < 0.8: intermediate value,
* 🟢 p(REC) ≤ 0.2: Hom LoF tolerant.
  {% endtab %}

{% tab title="RVIS ratio" %}
RVIS = Residual Variation Intolerance Score is indicative of a gene's intolerance to functional variation based on comparing the overall number of observed variants in a gene to the observed common functional variants.

Scale:

* 🔴 RVIS ≤ 30: functional variation intolerant,
* 🟠 RVIS > 30 & < 50: intermediate value,
* 🟢 RVIS ≥ 50: functional variation tolerant.
  {% endtab %}

{% tab title="pLoF o/e" %}
O/E Score is the ratio of the observed/expected number of LoF variants. It is a continuous measure of gene tolerance to LoF variation that incorporates a 90% confidence interval. The closer the O/E is to zero, the more likely the gene is LoF-constrained. If a hard threshold is needed for the interpretation of Mendelian disease cases, use the upper bound of the O/E confidence interval < 0.35.
{% endtab %}
{% endtabs %}

{% hint style="warning" %}
**Note:** Gene metrics card is not available for CNVs or mtDNA variants.
{% endhint %}


---

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