13-103051290-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000452.3(SLC10A2):​c.728T>A​(p.Leu243His) 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.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC10A2
NM_000452.3 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.06
Variant links:
Genes affected
SLC10A2 (HGNC:10906): (solute carrier family 10 member 2) This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A2NM_000452.3 linkc.728T>A p.Leu243His missense_variant Exon 4 of 6 ENST00000245312.5 NP_000443.2 Q12908

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC10A2ENST00000245312.5 linkc.728T>A p.Leu243His missense_variant Exon 4 of 6 1 NM_000452.3 ENSP00000245312.3 Q12908

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.51
D
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.77
T
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.2
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.019
D
Sift4G
Benign
0.36
T
Polyphen
0.97
D
Vest4
0.70
MutPred
0.55
Loss of stability (P = 0.0851);
MVP
0.91
MPC
0.014
ClinPred
0.91
D
GERP RS
5.5
Varity_R
0.23
gMVP
0.96

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: chr13-103703640; API