ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.9655A>T (p.Ile3219Phe) (rs771768835)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000735882 SCV000864095 uncertain significance not specified 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The ALMS1 c.9649A>T (p.Ile3217Phe, alternative name c.9655A>T) variant involves the alteration of a conserved nucleotide and 3/3 in silico tools (SNPsandGO not captured due to low reliability index and PolyPhen not working at time of scoring) predict a damaging outcome. However, these predictions have yet to be functionally assessed. This variant was found in 2/120722 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Invitae RCV001240879 SCV001413859 uncertain significance Alstrom syndrome 2019-05-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with phenylalanine at codon 3219 of the ALMS1 protein (p.Ile3219Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is present in population databases (rs771768835, ExAC 0.02%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 599293). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.

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