NRXN3 Gene Curation

Gene-disease assertions not curated here (add link or write note):

Disease	Autism
Inheritance	Autosomal dominant
Prevalence Possible sources Orphanet Medline Plus Genetics	Source:
Rapid or full curation?	Rapid Full
ClinGen / GenCC / BabySeq / HGMD / OMIM	GenCC- Ambry: Limited (AD Autism) SFARI- Category 1(High Confidence) for ASD
Clinical Validity Scoring Notes and points	Variant/Case Evidence: PMID: 22209245- Deletions described in 4 families. However, two are inherited from apparently unaffected family members while one is de novo and the 4th is inherited from a more mildly affected parent. If you don’t count those inherited (1pt + 1.5 pts = 2.5 pts) PMID: 35813072- p.R176* in individual with ASD, inherited from both with mild ID and speech/language delay (1 pt) Segregation Evidence: Case/Control Evidence: Experimental Evidence: Source:
Clinical Validity Points Total	Source:
Clinical Validity Classification Classifications (pts) Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed	LIMITED Source:
Molecular Mechanism Mechanisms Loss of function Gain of function Dominant negative Unknown Other	Loss of function / Gain of function / Dominant Negative
Penetrance options Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) (list source/PMID)	Source:
Age of Onset options Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID)
Severity Options Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete. Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high. Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced. Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low. None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.
Clinical Features	Sources:
HPO Terms https://hpo.jax.org/app/
Gene SOPs & Notes	LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant
Curation Summary Examples - The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Variable expression or severity: The severity and expressivity of the disorder is highly variable, even within families. - If multiple conditions associated with the gene: It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited
Case ID, Curator name, Date, Jira ticket link