rs60380298

chr13-103058285-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000452.3(SLC10A2):c.475G>A(p.Val159Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,601,868 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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. V159A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.022 (49 hom., cov: 32)
  • Exomes 𝑓: 0.019 (344 hom.)
• Consequence: SLC10A2 NM_000452.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.839

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024604201).
• BP6: Variant 13-103058285-C-T is Benign according to our data. Variant chr13-103058285-C-T is described in ClinVar as [Benign]. Clinvar id is 2122469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.022 (3344/152152) while in subpopulation AFR AF= 0.0278 (1152/41508). AF 95% confidence interval is 0.0264. There are 49 homozygotes in gnomad4. There are 1559 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.475G>A	p.Val159Ile	missense_variant	2/6	ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.475G>A	p.Val159Ile	missense_variant	2/6	1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3344 AN: 152034 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.0178 AC: 4466 AN: 251126 Hom.: 72 AF XY: 0.0172 AC XY: 2329 AN XY: 135690

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.00836

Gnomad ASJ exome AF: 0.0668

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00510

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0189 AC: 27403 AN: 1449716 Hom.: 344 Cov.: 29 AF XY: 0.0188 AC XY: 13592 AN XY: 722216

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.00866

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00468

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0197

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0220 AC: 3344 AN: 152152 Hom.: 49 Cov.: 32 AF XY: 0.0210 AC XY: 1559 AN XY: 74374

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0243 Hom.: 65

Bravo AF: 0.0220

TwinsUK AF: 0.0191 AC: 71

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.0295 AC: 130

ESP6500EA AF: 0.0251 AC: 216

ExAC AF: 0.0180 AC: 2179

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0237

EpiControl AF: 0.0223

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.55
Dann	Benign	0.80
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.029
Sift	Benign	0.18	T
Sift4G	Benign	0.54	T
Polyphen		0.0030	B
Vest4		0.027
MPC		0.0054
ClinPred		0.0047	T
GERP RS		-5.4
Varity_R		0.031
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs60380298; hg19: chr13-103710635; COSMIC: COSV55358929;