Genetic Variant SLCO1B3:p.Ala33Ser (chr12-20855040-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019844.4(SLCO1B3):c.97G>T(p.Ala33Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A33T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLCO1B3
NM_019844.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74

Publications

0 publications found

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 links:

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]

SLCO1B3-SLCO1B7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLCO1B3	NM_019844.4	MANE Select	c.97G>T	p.Ala33Ser	missense	Exon 4 of 16	NP_062818.1	Q9NPD5-1
SLCO1B3-SLCO1B7	NM_001371097.1		c.97G>T	p.Ala33Ser	missense	Exon 2 of 16	NP_001358026.1	A0A0A6YYJ9
SLCO1B3	NM_001349920.2		c.13G>T	p.Ala5Ser	missense	Exon 2 of 14	NP_001336849.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.97G>T	p.Ala33Ser	missense	Exon 4 of 16	ENSP00000370956.4	Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.97G>T	p.Ala33Ser	missense	Exon 2 of 16	ENSP00000441269.1
SLCO1B3	ENST00000261196.6	TSL:1	c.97G>T	p.Ala33Ser	missense	Exon 2 of 14	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.2

PhyloP100

3.7

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.22

Sift

Benign

0.047

Sift4G

Benign

0.12

Polyphen

0.97

Vest4

0.39

MutPred

0.68

Gain of catalytic residue at A33 (P = 0)

MVP

0.36

MPC

0.028

ClinPred

0.98

GERP RS

3.8

Varity_R

0.30

gMVP

0.45

Mutation Taster

=89/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over