Variant rs60140950 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_019844.4(SLCO1B3):c.767G>A(p.Gly256Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G256A) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLCO1B3
NM_019844.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.83

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:):

SLCO1B3-SLCO1B7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLCO1B3	NM_019844.4 linkuse as main transcript	c.767G>A	p.Gly256Glu	missense_variant	9/16	ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.767G>A	p.Gly256Glu	missense_variant	7/16
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.683G>A	p.Gly228Glu	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.767G>A	p.Gly256Glu	missense_variant	9/16	2	NM_019844.4	P1	Q9NPD5-1
SLCO1B3	ENST00000261196.6 linkuse as main transcript	c.767G>A	p.Gly256Glu	missense_variant	7/14	1		P1	Q9NPD5-1
SLCO1B3	ENST00000540853.5 linkuse as main transcript	c.767G>A	p.Gly256Glu	missense_variant	8/8	1
SLCO1B3	ENST00000544370.1 linkuse as main transcript	c.239G>A	p.Gly80Glu	missense_variant	3/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461060

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726836

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

.;T;T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

1.0

D;.;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.89

D;D;D;D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

4.2

.;H;H;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-7.5

D;D;D;D;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

.;D;D;.;.

Vest4

0.95, 0.95, 0.94

MutPred

0.65

Gain of catalytic residue at W258 (P = 0);Gain of catalytic residue at W258 (P = 0);Gain of catalytic residue at W258 (P = 0);.;Gain of catalytic residue at W258 (P = 0);

MVP

0.54

MPC

0.033, 0.045

ClinPred

1.0

GERP RS

3.9

Varity_R

0.97

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over