rs72547505

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000452.3(SLC10A2):c.785C>T(p.Thr262Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,613,904 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T262K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

SLC10A2
NM_000452.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:7B:1

Conservation

PhyloP100: 9.91

Publications

21 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.785C>T	p.Thr262Met	missense_variant	Exon 5 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.785C>T	p.Thr262Met	missense_variant	Exon 5 of 6	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000529

AC:

133

AN:

251356

AF XY:

0.000567

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000712

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000494

AC:

722

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000503

AC XY:

366

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33470

American (AMR)

AF:

0.000291

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

26132

East Asian (EAS)

AF:

0.000151

AC:

AN:

39682

South Asian (SAS)

AF:

0.000209

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000500

AC:

556

AN:

1111876

Other (OTH)

AF:

0.000480

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000512

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41510

American (AMR)

AF:

0.000524

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68022

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000700

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000511

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000415

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:7Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:4Benign:1

Feb 09, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PP3, PS3 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 23, 2018

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bile acid malabsorption, primary, 1

Uncertain:2

Mar 14, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Aug 04, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

SLC10A2-related disorder

Uncertain:1

May 16, 2024

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The SLC10A2 c.785C>T variant is predicted to result in the amino acid substitution p.Thr262Met. This variant was reported in a single individual with autosomal recessive primary bile acid malabsorption, but it was detected in cis (on the same chromosome) with a more rare variant (Oelkers et al. 1997. PubMed ID: 9109432). Functional studies have supported the pathogenicity of both changes alone, and as a complex allele, thus not allowing definitive conclusions about which may be causative (Ho et al. 2011. PubMed ID: 21649730). In ClinVar, this variant is interpreted by the majority of submitting laboratories as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/242727/evidence/). This variant is reported in 0.26% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.57

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

3.3

PhyloP100

9.9

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.98

MVP

0.93

MPC

0.022

ClinPred

0.27

GERP RS

5.7

Varity_R

0.74

gMVP

0.97

Mutation Taster

=14/86

disease causing

(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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rs72547505

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