ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.10754A>T (p.Gln3585Leu) (rs144486524)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224455 SCV000281198 likely benign not provided 2015-08-26 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV001084997 SCV000290062 likely benign Alstrom syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000436742 SCV000535048 likely benign not specified 2017-07-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445421 SCV000536991 likely benign Monogenic diabetes 2018-02-09 criteria provided, single submitter research ACMG criteria: BS2 (, BP4 (6 predictors), BP1 (most causal variants are truncating variants), Note:similar MAF in TODAY/1000G=likely benign
Genetic Services Laboratory,University of Chicago RCV000436742 SCV000593115 likely benign not specified 2017-02-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000436742 SCV000857952 benign not specified 2017-11-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000436742 SCV000864100 likely benign not specified 2018-11-12 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.10748A>T (p.Gln3583Leu, alternative name c.10754A>T) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00087 in 276312 control chromosomes, predominantly at a frequency of 0.0092 within the African subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 4-fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.10748A>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000436742 SCV000967144 likely benign not specified 2016-03-21 criteria provided, single submitter clinical testing p.Gln3583Leu in exon 16 of ALMS1: This variant is not expected to have clinical significance because it has been identified in 0.87% (84/9696) of African chromo somes by the Exome Aggregation Consortium (ExAC,; dbSNP rs144486524).

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