Submissions for variant NM_003060.4(SLC22A5):c.1590G>T (p.Met530Ile)

gnomAD frequency: 0.00335  dbSNP: rs148233131

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000552116	SCV000632539	benign	Renal carnitine transport defect	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001722466	SCV000731065	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	RCV000609684	SCV001363923	benign	not specified	2019-03-11	criteria provided, single submitter	clinical testing	Variant summary: SLC22A5 c.1590G>T (p.Met530Ile) results in a conservative amino acid change in 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 0.0011 in 277086 control chromosomes, predominantly at a frequency of 0.011 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 2.41 fold of 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.1590G>T 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) cite 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	RCV000552116	SCV002055882	benign	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Giacomini Lab, University of California, San Francisco	RCV000552116	SCV002576624	likely benign	Renal carnitine transport defect	2022-10-03	criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV001722466	SCV004161368	benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	SLC22A5: BP4, BS1, BS2