13-103052694-A-C

Position:

• chr13-103052694-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000245312.5(SLC10A2):​c.511T>G​(p.Ser171Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,603,298 control chromosomes in the GnomAD database, including 612,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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. S171D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.88 (59227 hom., cov: 31)
  • Exomes 𝑓: 0.87 (552896 hom.)
• Consequence: SLC10A2 ENST00000245312.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8493375E-6).
• BP6: Variant 13-103052694-A-C is Benign according to our data. Variant chr13-103052694-A-C is described in ClinVar as [Benign]. Clinvar id is 403446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-103052694-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC10A2	NM_000452.3	c.511T>G	p.Ser171Ala	missense_variant	3/6	ENST00000245312.5	NP_000443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5	c.511T>G	p.Ser171Ala	missense_variant	3/6	1	NM_000452.3	ENSP00000245312	P1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133943 AN: 152016 Hom.: 59176 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.869

GnomAD3 exomes AF: 0.854 AC: 214594 AN: 251138 Hom.: 92194 AF XY: 0.858 AC XY: 116395 AN XY: 135722

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.871

Gnomad EAS exome AF: 0.736

Gnomad SAS exome AF: 0.856

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.883

Gnomad OTH exome AF: 0.864

GnomAD4 exome AF: 0.872 AC: 1264980 AN: 1451164 Hom.: 552896 Cov.: 33 AF XY: 0.871 AC XY: 629678 AN XY: 722656

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.867

GnomAD4 genome AF: 0.881 AC: 134047 AN: 152134 Hom.: 59227 Cov.: 31 AF XY: 0.878 AC XY: 65294 AN XY: 74374

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.871

Alfa AF: 0.878 Hom.: 147784

Bravo AF: 0.877

TwinsUK AF: 0.883 AC: 3275

ALSPAC AF: 0.874 AC: 3368

ESP6500AA AF: 0.931 AC: 4102

ESP6500EA AF: 0.873 AC: 7505

ExAC AF: 0.861 AC: 104496

Asia WGS AF: 0.805 AC: 2801 AN: 3478

EpiCase AF: 0.878

EpiControl AF: 0.881

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

not specified Benign:1

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.33
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.028	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.74	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.066
MPC		0.0053
ClinPred		0.00049	T
GERP RS		5.8
Varity_R		0.068
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

Other links and lift over

dbSNP: rs188096; hg19: chr13-103705044; COSMIC: COSV55360754;