rs144020613
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_003060.4(SLC22A5):c.59T>A(p.Leu20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000662 in 1,613,396 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003060.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00335 AC: 509AN: 152156Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.00101 AC: 253AN: 249310Hom.: 1 AF XY: 0.000658 AC XY: 89AN XY: 135332
GnomAD4 exome AF: 0.000382 AC: 558AN: 1461122Hom.: 4 Cov.: 31 AF XY: 0.000323 AC XY: 235AN XY: 726924
GnomAD4 genome AF: 0.00335 AC: 510AN: 152274Hom.: 4 Cov.: 33 AF XY: 0.00329 AC XY: 245AN XY: 74470
ClinVar
Submissions by phenotype
Renal carnitine transport defect Uncertain:1Benign:2
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not provided Benign:2
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. -
SLC22A5: BS1, BS2 -
not specified Benign:1
Variant summary: SLC22A5 c.59T>A (p.Leu20His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 275576 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. c.59T>A has been reported in the literature in a cohort of subjects with a possible carnitine deficiency (Frigeni_2017). A functional study, Frigeni_2017, cites the variant with a transport activity of 46.77%, which the authors classify the variant as benign. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at