NM_019844.4:c.99C>T

Variant names:

• chr12-20855042-C-T
• rs144143469
• NM_019844.4:c.99C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_019844.4(SLCO1B3):​c.99C>T​(p.Ala33Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,610,268 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (2 hom.)
• Consequence: SLCO1B3 NM_019844.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0590
• Publications: 3 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.059 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.99C>T	p.Ala33Ala	synonymous	Exon 4 of 16	NP_062818.1	Q9NPD5-1
	SLCO1B3-SLCO1B7	NM_001371097.1		c.99C>T	p.Ala33Ala	synonymous	Exon 2 of 16	NP_001358026.1	A0A0A6YYJ9
	SLCO1B3	NM_001349920.2		c.15C>T	p.Ala5Ala	synonymous	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.99C>T	p.Ala33Ala	synonymous	Exon 4 of 16	ENSP00000370956.4	Q9NPD5-1
	SLCO1B3-SLCO1B7	ENST00000540229.1	TSL:2	c.99C>T	p.Ala33Ala	synonymous	Exon 2 of 16	ENSP00000441269.1
	SLCO1B3	ENST00000261196.6	TSL:1	c.99C>T	p.Ala33Ala	synonymous	Exon 2 of 14	ENSP00000261196.2	Q9NPD5-1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151978 Hom.: 0 Cov.: 32

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: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000273 AC: 68 AN: 249344 AF XY: 0.000349

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000119 AC: 174 AN: 1458290 Hom.: 2 Cov.: 30 AF XY: 0.000165 AC XY: 120 AN XY: 725386

African (AFR) AF: 0.0000301 AC: 1 AN: 33272

American (AMR) AF: 0.000136 AC: 6 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00134 AC: 115 AN: 85642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00156 AC: 7 AN: 4492

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111470

Other (OTH) AF: 0.0000665 AC: 4 AN: 60142

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.0000809 AC XY: 6 AN XY: 74210

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.0000642

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Rotor syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.7
DANN	Benign	0.42
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144143469; hg19: chr12-21007976;