rs72552731
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003060.4(SLC22A5):c.1161T>G(p.Tyr387Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003060.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.1161T>G | p.Tyr387Ter | stop_gained | 7/10 | ENST00000245407.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.1161T>G | p.Tyr387Ter | stop_gained | 7/10 | 1 | NM_003060.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Renal carnitine transport defect Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 20, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2023 | This sequence change creates a premature translational stop signal (p.Tyr387*) in the SLC22A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC22A5 are known to be pathogenic (PMID: 9916797). This variant is present in population databases (rs72552731, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with autosomal recessive primary carnitine deficiency (PMID: 12204000). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at