rs60380298

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000452.3(SLC10A2):c.475G>A(p.Val159Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,601,868 control chromosomes in the GnomAD database, including 393 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. V159A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 49 hom., cov: 32)

Exomes 𝑓: 0.019 ( 344 hom. )

Consequence

SLC10A2
NM_000452.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.839

Publications

17 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

SLC10A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024604201).

BP6

Variant 13-103058285-C-T is Benign according to our data. Variant chr13-103058285-C-T is described in ClinVar as Benign. ClinVar VariationId is 2122469.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.022 (3344/152152) while in subpopulation AFR AF = 0.0278 (1152/41508). AF 95% confidence interval is 0.0264. There are 49 homozygotes in GnomAd4. There are 1559 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.475G>A	p.Val159Ile	missense	Exon 2 of 6	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.475G>A	p.Val159Ile	missense	Exon 2 of 6	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3344

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0735

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0178

AC:

4466

AN:

251126

AF XY:

0.0172

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.00836

Gnomad ASJ exome

AF:

0.0668

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0189

AC:

27403

AN:

1449716

Hom.:

344

Cov.:

AF XY:

0.0188

AC XY:

13592

AN XY:

722216

show subpopulations

African (AFR)

AF:

0.0329

AC:

1092

AN:

33186

American (AMR)

AF:

0.00866

AC:

387

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

1748

AN:

26046

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39654

South Asian (SAS)

AF:

0.00468

AC:

403

AN:

86034

European-Finnish (FIN)

AF:

0.0118

AC:

628

AN:

53402

Middle Eastern (MID)

AF:

0.0369

AC:

212

AN:

5744

European-Non Finnish (NFE)

AF:

0.0197

AC:

21635

AN:

1100942

Other (OTH)

AF:

0.0216

AC:

1297

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1188

2376

3563

4751

5939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.0220

AC:

3344

AN:

152152

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

1559

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0278

AC:

1152

AN:

41508

American (AMR)

AF:

0.0124

AC:

189

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0735

AC:

255

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00395

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10600

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0220

AC:

1494

AN:

67996

Other (OTH)

AF:

0.0209

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

164

328

492

656

820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0232

Hom.:

144

Bravo

AF:

0.0220

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.0295

AC:

130

ESP6500EA

AF:

0.0251

AC:

216

ExAC

AF:

0.0180

AC:

2179

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0237

EpiControl

AF:

0.0223

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.55

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

-0.84

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.63

REVEL

Benign

0.029

Sift

Benign

0.18

Sift4G

Benign

0.54

Polyphen

0.0030

Vest4

0.027

MPC

0.0054

ClinPred

0.0047

GERP RS

-5.4

Varity_R

0.031

gMVP

0.82

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over