12-20855143-G-GT

Variant names:

• chr12-20855143-G-GT
• rs748195197
• NM_019844.4:c.203dupT

Variant summary

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

The NM_019844.4(SLCO1B3):​c.203dupT​(p.Leu68PhefsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,608,482 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SLCO1B3 NM_019844.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	NM_019844.4	MANE Select	c.203dupT	p.Leu68PhefsTer3	frameshift	Exon 4 of 16	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.203dupT	p.Leu68PhefsTer3	frameshift	Exon 2 of 16	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.119dupT	p.Leu40PhefsTer3	frameshift	Exon 2 of 14	NP_001336849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B3	ENST00000381545.8	TSL:2 MANE Select	c.203dupT	p.Leu68PhefsTer3	frameshift	Exon 4 of 16	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.203dupT	p.Leu68PhefsTer3	frameshift	Exon 2 of 16	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.203dupT	p.Leu68PhefsTer3	frameshift	Exon 2 of 14	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151930 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

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

GnomAD2 exomes AF: 0.00000814 AC: 2 AN: 245810 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000961 AC: 14 AN: 1456552 Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7 AN XY: 724620

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 43534

Ashkenazi Jewish (ASJ) AF: 0.000385 AC: 10 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 85522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.000188 AC: 1 AN: 5308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109950

Other (OTH) AF: 0.0000498 AC: 3 AN: 60188

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151930 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74178

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=30/170	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs748195197; hg19: chr12-21008077;