13-103052694-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000452.3(SLC10A2):​c.511T>C​(p.Ser171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. S171A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SLC10A2
NM_000452.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31203574).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A2NM_000452.3 linkc.511T>C p.Ser171Pro missense_variant Exon 3 of 6 ENST00000245312.5 NP_000443.2 Q12908

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC10A2ENST00000245312.5 linkc.511T>C p.Ser171Pro missense_variant Exon 3 of 6 1 NM_000452.3 ENSP00000245312.3 Q12908

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454092
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
724030
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.20
Sift
Benign
0.046
D
Sift4G
Benign
0.13
T
Polyphen
0.0030
B
Vest4
0.36
MutPred
0.61
Gain of glycosylation at S168 (P = 0.0683);
MVP
0.26
MPC
0.0073
ClinPred
0.44
T
GERP RS
5.8
Varity_R
0.84
gMVP
1.0

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: chr13-103705044; API