NM_001386879.1:c.1724G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001386879.1(SLCO1A2):​c.1724G>A​(p.Cys575Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD 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. C575S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLCO1A2
NM_001386879.1 missense

Scores

11
7
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLCO1A2NM_001386879.1 linkc.1724G>A p.Cys575Tyr missense_variant Exon 14 of 15 ENST00000683939.1 NP_001373808.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLCO1A2ENST00000683939.1 linkc.1724G>A p.Cys575Tyr missense_variant Exon 14 of 15 NM_001386879.1 ENSP00000508235.1 P46721-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.35
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
D;T
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Uncertain
0.75
D
MutationAssessor
Pathogenic
4.0
H;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-11
D;D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.98
MutPred
0.83
Gain of catalytic residue at L576 (P = 0);.;
MVP
0.77
MPC
0.33
ClinPred
1.0
D
GERP RS
4.3
Varity_R
0.98
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs762098103; hg19: chr12-21427472; API