12-20855111-AAGGAG-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_019844.4(SLCO1B3):c.170_174del(p.Arg57IlefsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R57R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SLCO1B3
NM_019844.4 frameshift
NM_019844.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.08
Genes affected
SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLCO1B3 | NM_019844.4 | c.170_174del | p.Arg57IlefsTer2 | frameshift_variant | 4/16 | ENST00000381545.8 | |
SLCO1B3-SLCO1B7 | NM_001371097.1 | c.170_174del | p.Arg57IlefsTer2 | frameshift_variant | 2/16 | ||
SLCO1B3 | NM_001349920.2 | c.86_90del | p.Arg29IlefsTer2 | frameshift_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLCO1B3 | ENST00000381545.8 | c.170_174del | p.Arg57IlefsTer2 | frameshift_variant | 4/16 | 2 | NM_019844.4 | P1 | |
SLCO1B3 | ENST00000261196.6 | c.170_174del | p.Arg57IlefsTer2 | frameshift_variant | 2/14 | 1 | P1 | ||
SLCO1B3 | ENST00000540853.5 | c.170_174del | p.Arg57IlefsTer2 | frameshift_variant | 3/8 | 1 | |||
SLCO1B3 | ENST00000545880.1 | n.22_26del | non_coding_transcript_exon_variant | 1/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rotor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 03, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.