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GeneBe

rs4149056

chr12-21178615-T-Achr12-21178615-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2_SupportingPM5PP3_Moderate

The NM_006446.5(SLCO1B1):c.521T>A(p.Val174Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. 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. V174A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SLCO1B1
NM_006446.5 missense

Scores

7
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.58

Links

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 33.
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr12-21178615-T-C is described in Lovd as [Pathogenic].
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLCO1B1NM_006446.5 linkuse as main transcriptc.521T>A p.Val174Glu missense_variant 6/15 ENST00000256958.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLCO1B1ENST00000256958.3 linkuse as main transcriptc.521T>A p.Val174Glu missense_variant 6/151 NM_006446.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.040
Cadd
Uncertain
26
Dann
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.42
Eigen_PC
Benign
0.19
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0078
T
MetaRNN
Pathogenic
0.90
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Pathogenic
3.7
H
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-5.8
D
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.83
MutPred
0.63
Loss of helix (P = 0.1299);
MVP
0.48
MPC
0.066
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.89
gMVP
0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-21331549;