13-103065958-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000452.3(SLC10A2):c.292G>A(p.Val98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,614,136 control chromosomes in the GnomAD database, including 1,180 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 68 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1112 hom. )

Consequence

SLC10A2
NM_000452.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.37

Publications

24 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003316313).

BP6

Variant 13-103065958-C-T is Benign according to our data. Variant chr13-103065958-C-T is described in ClinVar as Benign. ClinVar VariationId is 593350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0273 (4162/152294) while in subpopulation NFE AF = 0.0417 (2837/68010). AF 95% confidence interval is 0.0404. There are 68 homozygotes in GnomAd4. There are 1954 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 68 AR,Unknown 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.292G>A	p.Val98Ile	missense	Exon 1 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.292G>A	p.Val98Ile	missense	Exon 1 of 6	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4164

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00774

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0340

GnomAD2 exomes

AF:

0.0271

AC:

6820

AN:

251234

AF XY:

0.0267

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.0410

Gnomad OTH exome

AF:

0.0346

GnomAD4 exome

AF:

0.0366

AC:

53508

AN:

1461842

Hom.:

1112

Cov.:

AF XY:

0.0354

AC XY:

25776

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00609

AC:

204

AN:

33480

American (AMR)

AF:

0.0239

AC:

1068

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

374

AN:

26134

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.00371

AC:

320

AN:

86258

European-Finnish (FIN)

AF:

0.0422

AC:

2254

AN:

53416

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0426

AC:

47364

AN:

1111972

Other (OTH)

AF:

0.0310

AC:

1870

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

2914

5828

8743

11657

14571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1722

3444

5166

6888

8610

<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:

0.0273

AC:

4162

AN:

152294

Hom.:

Cov.:

AF XY:

0.0262

AC XY:

1954

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00772

AC:

321

AN:

41578

American (AMR)

AF:

0.0269

AC:

411

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00394

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10616

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0417

AC:

2837

AN:

68010

Other (OTH)

AF:

0.0337

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

205

410

616

821

1026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0354

Hom.:

316

Bravo

AF:

0.0269

TwinsUK

AF:

0.0477

AC:

177

ALSPAC

AF:

0.0457

AC:

176

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.0399

AC:

343

ExAC

AF:

0.0275

AC:

3343

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0365

EpiControl

AF:

0.0407

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.089

Eigen_PC

Benign

0.068

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.080

REVEL

Benign

0.12

Sift

Benign

0.75

Sift4G

Benign

0.82

Polyphen

0.45

Vest4

0.062

MPC

0.0057

ClinPred

0.027

GERP RS

5.3

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.16

gMVP

0.84

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over