5-132385381-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_003060.4(SLC22A5):āc.706T>Cā(p.Cys236Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C236F) has been classified as Uncertain significance.
Frequency
Consequence
NM_003060.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.706T>C | p.Cys236Arg | missense_variant | 4/10 | ENST00000245407.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.706T>C | p.Cys236Arg | missense_variant | 4/10 | 1 | NM_003060.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251486Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727162
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Renal carnitine transport defect Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 236 of the SLC22A5 protein (p.Cys236Arg). This variant is present in population databases (rs747050292, gnomAD 0.01%). This missense change has been observed in individual(s) with a positive newborn screening result for SLC22A5-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 575922). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | in vitro;research | Giacomini Lab, University of California, San Francisco | Oct 03, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 25, 2021 | The SLC22A5 c.706T>C; p.Cys236Arg variant (rs747050292), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 575922). This variant is found in the Latino population with an allele frequency of 0.01% (5/34592 alleles) in the Genome Aggregation Database. The cysteine at codon 236 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.754). However, given the lack of clinical and functional data, the significance of the p.Cys236Arg variant is uncertain at this time. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Decreased circulating carnitine concentration Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at