ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.10751A>T (p.Gln3584Leu)

gnomAD frequency: 0.00310  dbSNP: 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 2021-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000224455 SCV000535048 benign not provided 2020-05-18 criteria provided, single submitter clinical testing
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
Eurofins NTD LLC (GA) RCV000436742 SCV000857952 benign not specified 2017-11-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000436742 SCV000864100 benign not specified 2021-03-11 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.10748A>T (p.Gln3583Leu) 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 0.00066 in 248684 control chromosomes, predominantly at a frequency of 0.0094 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American 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 or African-American 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. Seven 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Laboratory for Molecular Medicine,Mass General Brigham 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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