12-20855073-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019844.4(SLCO1B3):​c.130G>T​(p.Gly44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLCO1B3
NM_019844.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0520
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]
SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18623492).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLCO1B3NM_019844.4 linkc.130G>T p.Gly44Cys missense_variant Exon 4 of 16 ENST00000381545.8 NP_062818.1 Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7NM_001371097.1 linkc.130G>T p.Gly44Cys missense_variant Exon 2 of 16 NP_001358026.1
SLCO1B3NM_001349920.2 linkc.46G>T p.Gly16Cys missense_variant Exon 2 of 14 NP_001336849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO1B3ENST00000381545.8 linkc.130G>T p.Gly44Cys missense_variant Exon 4 of 16 2 NM_019844.4 ENSP00000370956.4 Q9NPD5-1
SLCO1B3-SLCO1B7ENST00000540229.1 linkc.130G>T p.Gly44Cys missense_variant Exon 2 of 16 2 ENSP00000441269.1 A0A0A6YYJ9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250994
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1459806
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726280
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
0.010
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
15
DANN
Benign
0.80
DEOGEN2
Benign
0.17
.;T;T;.;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.81
T;.;T;T;T
M_CAP
Uncertain
0.088
D
MetaRNN
Benign
0.19
T;T;T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.3
.;M;M;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-4.7
D;D;D;D;D
REVEL
Benign
0.17
Sift
Benign
0.093
T;T;T;T;T
Sift4G
Benign
0.13
T;T;T;T;T
Polyphen
0.022
.;B;B;.;.
Vest4
0.28, 0.29, 0.26, 0.28
MutPred
0.54
Gain of catalytic residue at K49 (P = 0);Gain of catalytic residue at K49 (P = 0);Gain of catalytic residue at K49 (P = 0);Gain of catalytic residue at K49 (P = 0);Gain of catalytic residue at K49 (P = 0);
MVP
0.59
MPC
0.033, 0.044
ClinPred
0.10
T
GERP RS
-2.8
Varity_R
0.29
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1408642500; hg19: chr12-21008007; COSMIC: COSV53937278; COSMIC: COSV53937278; API