rs146185976
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The ENST00000245407.8(SLC22A5):c.852C>T(p.Leu284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )
Consequence
SLC22A5
ENST00000245407.8 synonymous
ENST00000245407.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.104
Genes affected
SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 5-132387052-C-T is Benign according to our data. Variant chr5-132387052-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 390633.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=3}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.852C>T | p.Leu284= | synonymous_variant | 5/10 | ENST00000245407.8 | NP_003051.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.852C>T | p.Leu284= | synonymous_variant | 5/10 | 1 | NM_003060.4 | ENSP00000245407 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000211 AC: 53AN: 251492Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135918
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GnomAD4 exome AF: 0.000312 AC: 456AN: 1461816Hom.: 0 Cov.: 32 AF XY: 0.000298 AC XY: 217AN XY: 727220
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74352
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 12, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2024 | In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge - |
Renal carnitine transport defect Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 10
Find out detailed SpliceAI scores and Pangolin per-transcript scores at