Submissions for variant NM_003060.4(SLC22A5):c.393+17G>A

gnomAD frequency: 0.02888  dbSNP: rs11568522

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000153960	SCV000171657	benign	not specified	2014-05-16	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.
Eurofins Ntd Llc (ga)	RCV000153960	SCV000203579	benign	not specified	2013-12-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000153960	SCV000920217	benign	not specified	2018-11-12	criteria provided, single submitter	clinical testing	Variant summary: SLC22A5 c.393+17G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.013 in 261426 control chromosomes in the gnomAD database, including 85 homozygotes. The observed variant frequency 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 benign. To our knowledge, no occurrence of c.393+17G>A in individuals affected with Systemic Primary Carnitine Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV000022313	SCV001723728	benign	Renal carnitine transport defect	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000022313	SCV002048135	benign	Renal carnitine transport defect	2023-10-02	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000022313	SCV002055868	benign	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing