chr13-103046191-G-T

Variant names:

• chr13-103046191-G-T
• rs758960672
• NM_000452.3:c.989C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000452.3(SLC10A2):​c.989C>A​(p.Thr330Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T330M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC10A2 NM_000452.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 5 publications found

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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055326223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	NM_000452.3	MANE Select	c.989C>A	p.Thr330Lys	missense	Exon 6 of 6	NP_000443.2	Q12908

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A2	ENST00000245312.5	TSL:1 MANE Select	c.989C>A	p.Thr330Lys	missense	Exon 6 of 6	ENSP00000245312.3	Q12908

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.014
DANN	Benign	0.21
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.037
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.0070
Sift	Benign	0.92	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.28		Gain of ubiquitination at T330 (P = 0.006)
MVP		0.12
MPC		0.0046
ClinPred		0.029	T
GERP RS		0.84
Varity_R		0.023
gMVP		0.36
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs758960672; hg19: chr13-103698541;