Variant 13-103065958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 593350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-103065958-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4162 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.292G>A	p.Val98Ile	missense_variant	1/6	ENST00000245312.5	NP_000443.2	Q12908

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 link	c.292G>A	p.Val98Ile	missense_variant	1/6	1	NM_000452.3	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

GnomAD3 exomes

AF:

0.0271

AC:

6820

AN:

251234

Hom.:

129

AF XY:

0.0267

AC XY:

3630

AN XY:

135756

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 SAS exome

AF:

0.00291

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

Gnomad4 AFR exome

AF:

0.00609

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0310

GnomAD4 genome

AF:

0.0273

AC:

4162

AN:

152294

Hom.:

Cov.:

AF XY:

0.0262

AC XY:

1954

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00772

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.0417

Gnomad4 OTH

AF:

0.0337

Alfa

AF:

0.0356

Hom.:

152

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

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

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

Varity_R

0.16

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over