ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.9652A>T (p.Ile3218Phe)

gnomAD frequency: 0.00001  dbSNP: rs771768835
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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 2022-07-31 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 3219 of the ALMS1 protein (p.Ile3219Phe). This variant is present in population databases (rs771768835, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 599293). 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.
GeneDx RCV002253599 SCV002525286 uncertain significance not provided 2022-05-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV001240879 SCV002786296 uncertain significance Alstrom syndrome 2022-04-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV003303226 SCV003999438 uncertain significance Cardiovascular phenotype 2023-05-03 criteria provided, single submitter clinical testing The p.I3219F variant (also known as c.9655A>T), located in coding exon 11 of the ALMS1 gene, results from an A to T substitution at nucleotide position 9655. The isoleucine at codon 3219 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001240879 SCV002078945 uncertain significance Alstrom syndrome 2021-10-05 no assertion criteria provided clinical testing

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