Submissions for variant NM_001134831.2(AHI1):c.2962-3T>C

gnomAD frequency: 0.00013  dbSNP: rs369713977

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000321916	SCV000460479	uncertain significance	Joubert syndrome 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001317183	SCV001507832	uncertain significance	Familial aplasia of the vermis	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change falls in intron 20 of the AHI1 gene. It does not directly change the encoded amino acid sequence of the AHI1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369713977, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with AHI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 355497). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002523550	SCV003555786	uncertain significance	Inborn genetic diseases	2022-11-14	criteria provided, single submitter	clinical testing	The c.2962-3T>C intronic alteration consists of a T to C substitution 3 nucleotides before coding exon 19 in the AHI1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000321916	SCV003823072	uncertain significance	Joubert syndrome 3	2022-04-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004752875	SCV005353595	likely benign	AHI1-related disorder	2024-05-15	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).