rs188096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000452.3(SLC10A2):c.511T>G(p.Ser171Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,603,298 control chromosomes in the GnomAD database, including 612,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S171D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.88 ( 59227 hom., cov: 31)

Exomes 𝑓: 0.87 ( 552896 hom. )

Consequence

SLC10A2
NM_000452.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.26

Publications

53 publications found

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]

SLC10A2 Gene-Disease associations (from GenCC):

bile acid malabsorption, primary, 1
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC10A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8493375E-6).

BP6

Variant 13-103052694-A-C is Benign according to our data. Variant chr13-103052694-A-C is described in ClinVar as Benign. ClinVar VariationId is 403446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.511T>G	p.Ser171Ala	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
SLC10A2	ENST00000245312.5 link	c.511T>G	p.Ser171Ala	missense_variant	Exon 3 of 6	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

133943

AN:

152016

Hom.:

59176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.975

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.867

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.842

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.869

GnomAD2 exomes

AF:

0.854

AC:

214594

AN:

251138

AF XY:

0.858

show subpopulations

Gnomad AFR exome

AF:

0.930

Gnomad AMR exome

AF:

0.762

Gnomad ASJ exome

AF:

0.871

Gnomad EAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.883

Gnomad NFE exome

AF:

0.883

Gnomad OTH exome

AF:

0.864

GnomAD4 exome

AF:

0.872

AC:

1264980

AN:

1451164

Hom.:

552896

Cov.:

AF XY:

0.871

AC XY:

629678

AN XY:

722656

show subpopulations

African (AFR)

AF:

0.932

AC:

30996

AN:

33242

American (AMR)

AF:

0.765

AC:

34205

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

22686

AN:

26062

East Asian (EAS)

AF:

0.723

AC:

28659

AN:

39626

South Asian (SAS)

AF:

0.855

AC:

73586

AN:

86052

European-Finnish (FIN)

AF:

0.885

AC:

47287

AN:

53406

Middle Eastern (MID)

AF:

0.869

AC:

4995

AN:

5748

European-Non Finnish (NFE)

AF:

0.880

AC:

970536

AN:

1102336

Other (OTH)

AF:

0.867

AC:

52030

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

7312

14624

21936

29248

36560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21042

42084

63126

84168

105210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.881

AC:

134047

AN:

152134

Hom.:

59227

Cov.:

AF XY:

0.878

AC XY:

65294

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.930

AC:

38604

AN:

41494

American (AMR)

AF:

0.811

AC:

12394

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

3007

AN:

3470

East Asian (EAS)

AF:

0.737

AC:

3805

AN:

5166

South Asian (SAS)

AF:

0.842

AC:

4050

AN:

4812

European-Finnish (FIN)

AF:

0.880

AC:

9321

AN:

10592

Middle Eastern (MID)

AF:

0.839

AC:

245

AN:

292

European-Non Finnish (NFE)

AF:

0.881

AC:

59894

AN:

68010

Other (OTH)

AF:

0.871

AC:

1838

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

810

1621

2431

3242

4052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.878

Hom.:

279388

Bravo

AF:

0.877

TwinsUK

AF:

0.883

AC:

3275

ALSPAC

AF:

0.874

AC:

3368

ESP6500AA

AF:

0.931

AC:

4102

ESP6500EA

AF:

0.873

AC:

7505

ExAC

AF:

0.861

AC:

104496

Asia WGS

AF:

0.805

AC:

2801

AN:

3478

EpiCase

AF:

0.878

EpiControl

AF:

0.881

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.0

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.035

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.028

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.74

PhyloP100

1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

0.47

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.066

MPC

0.0053

ClinPred

0.00049

GERP RS

5.8

Varity_R

0.068

gMVP

0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over