chr12-20855111-AAGGAG-A
Position:
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.