chr13-103049340-G-A

Position:

chr13-103049340-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The ENST00000245312.5(SLC10A2):c.868C>T(p.Pro290Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,978 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P290L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0087 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

SLC10A2
ENST00000245312.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 9.91

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 -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, BayesDel_noAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0128285885).

BP6

Variant 13-103049340-G-A is Benign according to our data. Variant chr13-103049340-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 374538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3 linkuse as main transcript	c.868C>T	p.Pro290Ser	missense_variant	5/6	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 linkuse as main transcript	c.868C>T	p.Pro290Ser	missense_variant	5/6	1	NM_000452.3	ENSP00000245312	P1

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1330

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00998

AC:

2508

AN:

251256

Hom.:

AF XY:

0.0101

AC XY:

1367

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.00716

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0106

AC:

15488

AN:

1461696

Hom.:

120

Cov.:

AF XY:

0.0105

AC XY:

7613

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00629

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00873

AC:

1329

AN:

152282

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

615

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00960

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00955

AC:

1159

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0155

EpiControl

AF:

0.0178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 in 1000Genomes: 22/2178=1% -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	SLC10A2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.54

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.33

Sift

Uncertain

0.011

Sift4G

Benign

0.069

Polyphen

0.99

Vest4

0.91

MVP

0.58

MPC

0.012

ClinPred

0.041

GERP RS

5.7

Varity_R

0.50

gMVP

0.91

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