rs386134194
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_003060.4(SLC22A5):c.453G>A(p.Val151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,130 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). Synonymous variant affecting the same amino acid position (i.e. V151V) has been classified as Likely benign.
Frequency
Consequence
NM_003060.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC22A5 | NM_003060.4 | c.453G>A | p.Val151= | synonymous_variant | 2/10 | ENST00000245407.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC22A5 | ENST00000245407.8 | c.453G>A | p.Val151= | synonymous_variant | 2/10 | 1 | NM_003060.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251496Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135922
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727248
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74378
ClinVar
Submissions by phenotype
Renal carnitine transport defect Pathogenic:3Uncertain:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 26, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genomics Program, Stanford Medicine | Jan 10, 2019 | The p.Val151= variant in the SLC22A5 gene has been seen previously in 3 individuals with primary systemic carnitine deficiency (unpublished, ARUP Primary Carnitine Deficiency and SLC22A5 Database). In two of these patients, a second likely pathogenic/pathogenic variant was identified [Thr440Met; Pro46Ser], consistent with autosomal recessive inheritence. The p.Val151= variant has been identified in 11/129200 non-Finnish European alleles by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational splicing tools predict formation of a cryptic splice site; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Val151= variant is uncertain. However, there is suspicion that this variant could be associated with primary systemic carnitine deficiency as it has been seen in 3 other affected individuals. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2, PM3, PP3] - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change affects codon 151 of the SLC22A5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SLC22A5 protein. This variant is present in population databases (rs386134194, gnomAD 0.009%). This variant has been observed in individual(s) with primary carnitine deficiency (PMID: 28841266; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 25375). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | Mar 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at