12-20815821-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019844.4(SLCO1B3):ā€‹c.83A>Gā€‹(p.Lys28Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,572,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

SLCO1B3
NM_019844.4 missense, splice_region

Scores

3
16
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLCO1B3NM_019844.4 linkc.83A>G p.Lys28Arg missense_variant, splice_region_variant Exon 3 of 16 ENST00000381545.8 NP_062818.1 Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7NM_001371097.1 linkc.83A>G p.Lys28Arg missense_variant, splice_region_variant Exon 1 of 16 NP_001358026.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO1B3ENST00000381545.8 linkc.83A>G p.Lys28Arg missense_variant, splice_region_variant Exon 3 of 16 2 NM_019844.4 ENSP00000370956.4 Q9NPD5-1
SLCO1B3-SLCO1B7ENST00000540229.1 linkc.83A>G p.Lys28Arg missense_variant, splice_region_variant Exon 1 of 16 2 ENSP00000441269.1 A0A0A6YYJ9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.04e-7
AC:
1
AN:
1419706
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
706144
show subpopulations
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:
9.20e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152350
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;T;T;.;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.74
T;.;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.14
T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.6
.;L;L;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.6
N;N;N;N;N
REVEL
Benign
0.086
Sift
Uncertain
0.023
D;D;D;D;T
Sift4G
Uncertain
0.044
D;D;D;D;D
Polyphen
0.61
.;P;P;.;.
Vest4
0.30, 0.33, 0.35
MutPred
0.55
Loss of methylation at K28 (P = 0.0108);Loss of methylation at K28 (P = 0.0108);Loss of methylation at K28 (P = 0.0108);Loss of methylation at K28 (P = 0.0108);Loss of methylation at K28 (P = 0.0108);
MVP
0.55
MPC
0.012, 0.012
ClinPred
0.38
T
GERP RS
0.69
Varity_R
0.17
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.96
SpliceAI score (max)
0.19
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: rs563634489; hg19: chr12-20968755; API