chr12-20855111-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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
Variant links:
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]

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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
SLCO1B3NM_019844.4 linkuse as main transcriptc.170_174del p.Arg57IlefsTer2 frameshift_variant 4/16 ENST00000381545.8
SLCO1B3-SLCO1B7NM_001371097.1 linkuse as main transcriptc.170_174del p.Arg57IlefsTer2 frameshift_variant 2/16
SLCO1B3NM_001349920.2 linkuse as main transcriptc.86_90del p.Arg29IlefsTer2 frameshift_variant 2/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B3ENST00000381545.8 linkuse as main transcriptc.170_174del p.Arg57IlefsTer2 frameshift_variant 4/162 NM_019844.4 P1Q9NPD5-1
SLCO1B3ENST00000261196.6 linkuse as main transcriptc.170_174del p.Arg57IlefsTer2 frameshift_variant 2/141 P1Q9NPD5-1
SLCO1B3ENST00000540853.5 linkuse as main transcriptc.170_174del p.Arg57IlefsTer2 frameshift_variant 3/81
SLCO1B3ENST00000545880.1 linkuse as main transcriptn.22_26del non_coding_transcript_exon_variant 1/45

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 submitterclinical testingRevvity Omics, RevvityNov 03, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21008045; API