chr12-20855146-T-TAATTG
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_019844.4(SLCO1B3):c.205_209dupATTGA(p.Asp70GlufsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,609,310 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_019844.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLCO1B3 | NM_019844.4 | c.205_209dupATTGA | p.Asp70GlufsTer13 | frameshift_variant | Exon 4 of 16 | ENST00000381545.8 | NP_062818.1 | |
SLCO1B3-SLCO1B7 | NM_001371097.1 | c.205_209dupATTGA | p.Asp70GlufsTer13 | frameshift_variant | Exon 2 of 16 | NP_001358026.1 | ||
SLCO1B3 | NM_001349920.2 | c.121_125dupATTGA | p.Asp42GlufsTer13 | frameshift_variant | Exon 2 of 14 | NP_001336849.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLCO1B3 | ENST00000381545.8 | c.205_209dupATTGA | p.Asp70GlufsTer13 | frameshift_variant | Exon 4 of 16 | 2 | NM_019844.4 | ENSP00000370956.4 | ||
SLCO1B3-SLCO1B7 | ENST00000540229.1 | c.205_209dupATTGA | p.Asp70GlufsTer13 | frameshift_variant | Exon 2 of 16 | 2 | ENSP00000441269.1 |
Frequencies
GnomAD3 genomes AF: 0.00380 AC: 579AN: 152236Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00416 AC: 1024AN: 245910Hom.: 9 AF XY: 0.00409 AC XY: 544AN XY: 132962
GnomAD4 exome AF: 0.00348 AC: 5072AN: 1456956Hom.: 27 Cov.: 30 AF XY: 0.00347 AC XY: 2518AN XY: 724844
GnomAD4 genome AF: 0.00380 AC: 579AN: 152354Hom.: 7 Cov.: 32 AF XY: 0.00447 AC XY: 333AN XY: 74496
ClinVar
Submissions by phenotype
Rotor syndrome Pathogenic:1Uncertain:1
- -
The SLCO1B3 c.205_209dup; p.Asp70GlufsTer13 variant (rs558592800, ClinVar Variation ID: 712105) is reported in the literature as one among several variants in one family with autism spectrum disorder, but with no details on hemolytic anemia or related phenotype (Yuen 2015). This variant is found in the Finnish European population with an allele frequency of 2.0% (499/24964 alleles, including 8 homozygotes) in the Genome Aggregation Database (v2.1.1). This variant causes a frameshift by inserting 5 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Since the mechanism of pathogenicity for SLCO1B3 is by loss-of-function, this variant is considered to be pathogenic. References: Yuen RK et al., Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med. 2015 Feb;21(2):185-91. PMID: 25621899. -
not provided Benign:1
- -
SLCO1B3-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at