Submissions for variant NM_031418.4(ANO3):c.1231A>G (p.Ile411Val)

gnomAD frequency: 0.00030  dbSNP: rs767864233

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002070233	SCV002430360	benign	Dystonic disorder	2024-04-22	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356278	SCV001551400	uncertain significance	Dystonia 24		no assertion criteria provided	clinical testing	The ANO3 p.I411V variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs767864233) and in control databases in 47 of 250996 chromosomes at a frequency of 0.0001873, and was observed at the highest frequency in the Latino population in 46 of 34520 chromosomes (freq: 0.001333) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.I411 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; however this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003898338	SCV004717085	likely benign	ANO3-related disorder	2022-04-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).