Submissions for variant NM_001378454.1(ALMS1):c.10628C>G (p.Thr3543Ser)

gnomAD frequency: 0.00688  dbSNP: rs45501594

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001079318	SCV000262122	benign	Alstrom syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224685	SCV000280969	likely benign	not provided	2015-09-29	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000224685	SCV000531893	benign	not provided	2018-07-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26239645, 25846608)
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445553	SCV000536990	benign	Monogenic diabetes	2019-02-01	criteria provided, single submitter	research	ACMG criteria: BP4 (six predictors plus Revel score: 0.024; not using PP3's three predictors), BA1 (1% in gnomAD European population), BS2 (15 homozygotes in gnomAD), BP1 (missense variant when mostly truncating mutations)= benign
Eurofins Ntd Llc (ga)	RCV000434829	SCV000705014	benign	not specified	2017-01-25	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000434829	SCV000711946	benign	not specified	2017-12-14	criteria provided, single submitter	clinical testing	p.Thr3542Ser in exon 16 of ALMS1: This variant is not expected to have clinical significance because it has been identified in 1.03% (1297/125086) of European c hromosomes including 12 homozygotes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs45501594).
Athena Diagnostics Inc	RCV000224685	SCV000840768	benign	not provided	2018-07-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000434829	SCV000864099	benign	not specified	2016-08-02	criteria provided, single submitter	clinical testing	Variant summary: The ALMS1 c.10625C>G (p.Thr3542Ser, alternative name c.10631C>G) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant. This variant was found in 824/119494 control chromosomes (5 homozygotes), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0099462 (658/66156). This frequency is about 4 to 7 times the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361) for CYMO or Alstrom Syndrom, respectively. The allele frequency in the European (Non-Finnish) subpopulation suggests that this variant is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. The variant has been reported in patients with clinical features of Alstrom Syndrome, but without evidence of causality (ie co-segregation or functional studies). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV002408898	SCV002711112	benign	Cardiovascular phenotype	2019-01-03	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001079318	SCV002758759	uncertain significance	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 rs45501594 in Alstrom syndrome yet.
CeGaT Center for Human Genetics Tuebingen	RCV000224685	SCV004155005	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	ALMS1: BP4, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001079318	SCV004563919	benign	Alstrom syndrome	2023-08-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001079318	SCV002078979	benign	Alstrom syndrome	2019-12-02	no assertion criteria provided	clinical testing