12-20855143-G-GT
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_019844.4(SLCO1B3):c.203dupT(p.Leu68PhefsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,608,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_019844.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLCO1B3 | NM_019844.4 | c.203dupT | p.Leu68PhefsTer3 | frameshift_variant | Exon 4 of 16 | ENST00000381545.8 | NP_062818.1 | |
SLCO1B3-SLCO1B7 | NM_001371097.1 | c.203dupT | p.Leu68PhefsTer3 | frameshift_variant | Exon 2 of 16 | NP_001358026.1 | ||
SLCO1B3 | NM_001349920.2 | c.119dupT | p.Leu40PhefsTer3 | frameshift_variant | Exon 2 of 14 | NP_001336849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLCO1B3 | ENST00000381545.8 | c.203dupT | p.Leu68PhefsTer3 | frameshift_variant | Exon 4 of 16 | 2 | NM_019844.4 | ENSP00000370956.4 | ||
SLCO1B3-SLCO1B7 | ENST00000540229.1 | c.203dupT | p.Leu68PhefsTer3 | frameshift_variant | Exon 2 of 16 | 2 | ENSP00000441269.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151930Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245810Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 132896
GnomAD4 exome AF: 0.00000961 AC: 14AN: 1456552Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7AN XY: 724620
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151930Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74178
ClinVar
Submissions by phenotype
Rotor syndrome Uncertain:1
The SLCO1B1 c.203dupT (p.Leu68PhefsTer3) variant results in a frameshift, and is predicted to cause an elongation of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.000208 in the Ashkenazi Jewish population from the Genome Aggregation Database, however this is based on two alleles so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for Rotor syndrome. Note: bi-allelic variants in both the SLCO1B1 and SLCO1B3 genes combined have been shown to cause Rotor syndrome. For an individual to be affected with Rotor syndrome, they must carry a pathogenic variant in both copies of the SLCO1B1 gene and in both copies of the SLCO1B3 gene. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at