Submissions for variant NM_001378454.1(ALMS1):c.10272G>C (p.Lys3424Asn)

gnomAD frequency: 0.00566  dbSNP: rs34398445

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001084442	SCV000290060	benign	Alstrom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000434583	SCV000510877	benign	not provided	2016-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000438106	SCV000534464	benign	not specified	2016-12-27	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	RCV000445397	SCV000536988	benign	Monogenic diabetes	2018-10-12	criteria provided, single submitter	research	ACMG criteria: BP1 (disease caused by truncating variants), BA1 (1.9% in gnomAD African), BS2 (6 homozygotes in gnomAD African), BP4 (7 predictors + REVEL 0.039)= benign
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000438106	SCV000711801	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Lys3423Asn in exon 15 of ALMS1: This variant is not expected to have clinical significance because it has been identified in 3.03% (40/1322) of African chromo somes by the 1000 Genomes Project (Phase 3; dbSNP rs34398445).
Athena Diagnostics Inc	RCV000434583	SCV000840766	likely benign	not provided	2018-05-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000438106	SCV000864097	benign	not specified	2017-02-06	criteria provided, single submitter	clinical testing	Variant summary: The ALMS1 c.10269G>C (p.Lys3423Asn, alternative name c.10275G>C) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 3/5 in silico tools. This variant was found in 211/120598 control chromosomes (including four homozygotes), predominantly observed in the African subpopulation at a frequency of 0.019804 (194/9796). This frequency is about 9 times the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. It has not, to our knowledge, been reported in affected individuals in literature. One clinical diagnostic laboratory has classified this variant as benign. Taken together this variant is classified as benign variant.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001084442	SCV002605264	likely benign	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 rs34398445 in Alstrom syndrome yet.
Ambry Genetics	RCV002379015	SCV002692094	benign	Cardiovascular phenotype	2018-12-24	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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000434583	SCV001798187	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000438106	SCV001923851	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000438106	SCV001926808	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000434583	SCV001965534	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001084442	SCV002078968	benign	Alstrom syndrome	2019-12-05	no assertion criteria provided	clinical testing