rs780129415
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong
The NM_003060.4(SLC22A5):c.1515C>T(p.Leu505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,614,058 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
SLC22A5
NM_003060.4 synonymous
NM_003060.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.938
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 Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 5-132393740-C-T is Benign according to our data. Variant chr5-132393740-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 529856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.1515C>T | p.Leu505= | synonymous_variant | 9/10 | ENST00000245407.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.1515C>T | p.Leu505= | synonymous_variant | 9/10 | 1 | NM_003060.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251444Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135888
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.0000591 AC XY: 43AN XY: 727234
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SLC22A5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 13, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Renal carnitine transport defect Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 17
Find out detailed SpliceAI scores and Pangolin per-transcript scores at