Submissions for variant NM_003060.4(SLC22A5):c.1249A>G (p.Met417Val)

gnomAD frequency: 0.00365  dbSNP: rs139775414

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000555770	SCV000632519	benign	Renal carnitine transport defect	2025-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001696988	SCV000731064	benign	not provided	2020-08-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24123366)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000602546	SCV001363925	benign	not specified	2019-03-11	criteria provided, single submitter	clinical testing	Variant summary: SLC22A5 c.1249A>G (p.Met417Val) results in a conservative amino acid change located in the Major facilitator superfamily domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 277134 control chromosomes, predominantly at a frequency of 0.012 within the African subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in SLC22A5 causing Systemic Primary Carnitine Deficiency phenotype (0.0046), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1249A>G in individuals affected with Systemic Primary Carnitine Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant once as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV000555770	SCV002055878	benign	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Giacomini Lab, University of California, San Francisco	RCV000555770	SCV002576600	likely benign	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV001696988	SCV004011618	benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	SLC22A5: BP4, BS1, BS2