ClinVar Miner

Submissions for variant NM_000081.4(LYST):c.3250G>A (p.Ala1084Thr)

gnomAD frequency: 0.00001  dbSNP: rs376496670
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001905687 SCV002155980 uncertain significance Chédiak-Higashi syndrome 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1084 of the LYST protein (p.Ala1084Thr). This variant is present in population databases (rs376496670, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 1386113). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002264416 SCV002543624 uncertain significance Autoinflammatory syndrome 2018-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002552939 SCV003651545 uncertain significance Inborn genetic diseases 2022-09-29 criteria provided, single submitter clinical testing The c.3250G>A (p.A1084T) alteration is located in exon 6 (coding exon 4) of the LYST gene. This alteration results from a G to A substitution at nucleotide position 3250, causing the alanine (A) at amino acid position 1084 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001905687 SCV003812797 uncertain significance Chédiak-Higashi syndrome 2019-06-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987930 SCV004803511 uncertain significance not specified 2024-01-18 criteria provided, single submitter clinical testing Variant summary: LYST c.3250G>A (p.Ala1084Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250912 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3250G>A in individuals affected with Chediak-Higashi Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1386113). Based on the evidence outlined above, the variant was classified as uncertain significance.

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