ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.3095C>G (p.Thr1032Ser) (rs199922877)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000418778 SCV000232740 uncertain significance not provided 2015-02-17 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000418778 SCV000511342 likely benign not provided 2016-09-01 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
GeneDx RCV000418778 SCV000573685 uncertain significance not provided 2018-08-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The T1032S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 29/30774 (0.09%) alleles from individuals of South Asian ancestry and in 39/126034 (0.03%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The T1032S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000634783 SCV000756126 uncertain significance Alstrom syndrome 2017-09-22 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1032 of the ALMS1 protein (p.Thr1032Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs199922877, ExAC 0.08%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 198870). 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.