chr12-20855073-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019844.4(SLCO1B3):​c.130G>A​(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLCO1B3
NM_019844.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05848658).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B3NM_019844.4 linkuse as main transcriptc.130G>A p.Gly44Ser missense_variant 4/16 ENST00000381545.8
SLCO1B3-SLCO1B7NM_001371097.1 linkuse as main transcriptc.130G>A p.Gly44Ser missense_variant 2/16
SLCO1B3NM_001349920.2 linkuse as main transcriptc.46G>A p.Gly16Ser missense_variant 2/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B3ENST00000381545.8 linkuse as main transcriptc.130G>A p.Gly44Ser missense_variant 4/162 NM_019844.4 P1Q9NPD5-1
SLCO1B3ENST00000261196.6 linkuse as main transcriptc.130G>A p.Gly44Ser missense_variant 2/141 P1Q9NPD5-1
SLCO1B3ENST00000540853.5 linkuse as main transcriptc.130G>A p.Gly44Ser missense_variant 3/81
SLCO1B3ENST00000545880.1 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152106
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250994
Hom.:
0
AF XY:
0.00
AC XY:
0
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
AF:
0.00000137
AC:
2
AN:
1459808
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726280
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022The c.130G>A (p.G44S) alteration is located in exon 3 (coding exon 2) of the SLCO1B3 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the glycine (G) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
1.6
DANN
Benign
0.33
DEOGEN2
Benign
0.056
.;T;T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.76
T;.;T;T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.058
T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
-0.050
.;N;N;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.9
N;N;N;N;N
REVEL
Benign
0.086
Sift
Benign
1.0
T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0030
.;B;B;.;.
Vest4
0.17, 0.17, 0.14, 0.20
MutPred
0.50
Gain of catalytic residue at K49 (P = 0.0026);Gain of catalytic residue at K49 (P = 0.0026);Gain of catalytic residue at K49 (P = 0.0026);Gain of catalytic residue at K49 (P = 0.0026);Gain of catalytic residue at K49 (P = 0.0026);
MVP
0.40
MPC
0.0077, 0.010
ClinPred
0.050
T
GERP RS
-2.8
Varity_R
0.11
gMVP
0.25

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: COSV53942791; COSMIC: COSV53942791; API