chr12-20815742-G-A

Variant summary

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

The NM_019844.4(SLCO1B3):​c.4G>A​(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,422,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLCO1B3
NM_019844.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
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 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=0.21166629).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B3NM_019844.4 linkuse as main transcriptc.4G>A p.Asp2Asn missense_variant 3/16 ENST00000381545.8
SLCO1B3-SLCO1B7NM_001371097.1 linkuse as main transcriptc.4G>A p.Asp2Asn missense_variant 1/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B3ENST00000381545.8 linkuse as main transcriptc.4G>A p.Asp2Asn missense_variant 3/162 NM_019844.4 P1Q9NPD5-1
SLCO1B3ENST00000261196.6 linkuse as main transcriptc.4G>A p.Asp2Asn missense_variant 1/141 P1Q9NPD5-1
SLCO1B3ENST00000540853.5 linkuse as main transcriptc.4G>A p.Asp2Asn missense_variant 2/81

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000141
AC:
2
AN:
1422388
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
708142
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:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
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 GeneticsApr 11, 2023The c.4G>A (p.D2N) alteration is located in exon 2 (coding exon 1) of the SLCO1B3 gene. This alteration results from a G to A substitution at nucleotide position 4, causing the aspartic acid (D) at amino acid position 2 to be replaced by an asparagine (N). 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
0.092
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T;T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.56
T;.;T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.21
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M;M;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.8
N;N;N;N;N
REVEL
Benign
0.073
Sift
Benign
0.21
T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T
Polyphen
0.31
.;B;B;.;.
Vest4
0.20, 0.20, 0.26, 0.35
MutPred
0.29
Gain of MoRF binding (P = 0.0884);Gain of MoRF binding (P = 0.0884);Gain of MoRF binding (P = 0.0884);Gain of MoRF binding (P = 0.0884);Gain of MoRF binding (P = 0.0884);
MVP
0.43
MPC
0.012, 0.023
ClinPred
0.84
D
GERP RS
2.1
Varity_R
0.058
gMVP
0.35

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: rs763219424; hg19: chr12-20968676; COSMIC: COSV99681252; API