ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12103G>A (p.Ala4035Thr)

gnomAD frequency: 0.00006  dbSNP: rs757364858
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Personalized Diabetes Medicine Program, University of Maryland School of Medicine RCV001172504 SCV001335557 likely benign Monogenic diabetes 2019-02-22 criteria provided, single submitter research ACMG criteria: BP4 (REVEL 0.085 + 5 predictors), BP1 = likely benign
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001328464 SCV001519611 uncertain significance not specified 2021-03-11 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.12100G>A (p.Ala4034Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 249478 control chromosomes. 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.12100G>A in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001833728 SCV002162039 uncertain significance Alstrom syndrome 2022-06-23 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 4036 of the ALMS1 protein (p.Ala4036Thr). This variant is present in population databases (rs757364858, gnomAD 0.01%). 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: 916711). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV001833728 SCV003928180 likely risk allele Alstrom syndrome criteria provided, single submitter research Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs757364858 in Alstrom syndrome yet.
Natera, Inc. RCV001833728 SCV002079052 uncertain significance Alstrom syndrome 2021-07-21 no assertion criteria provided clinical testing

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.