Genetic Variant NM_000452.3:c.129C>T (chr13-103066121-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000452.3(SLC10A2):c.129C>T(p.Ala43Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,614,020 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 64 hom., cov: 32)

Exomes 𝑓: 0.019 ( 338 hom. )

Consequence

SLC10A2
NM_000452.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.193

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

bile acid malabsorption, primary, 1
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC10A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 13-103066121-G-A is Benign according to our data. Variant chr13-103066121-G-A is described in ClinVar as Benign. ClinVar VariationId is 2122470.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.193 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0242 (3690/152230) while in subpopulation AFR AF = 0.0361 (1500/41546). AF 95% confidence interval is 0.0346. There are 64 homozygotes in GnomAd4. There are 1712 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A2	NM_000452.3 link	c.129C>T	p.Ala43Ala	synonymous_variant	Exon 1 of 6	ENST00000245312.5	NP_000443.2	Q12908

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC10A2	ENST00000245312.5 link	c.129C>T	p.Ala43Ala	synonymous_variant	Exon 1 of 6	1	NM_000452.3	ENSP00000245312.3		Q12908

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3691

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0362

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.0730

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0548

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0240

GnomAD2 exomes

AF:

0.0185

AC:

4649

AN:

251448

AF XY:

0.0178

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.00824

Gnomad ASJ exome

AF:

0.0640

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0192

AC:

28125

AN:

1461790

Hom.:

338

Cov.:

AF XY:

0.0191

AC XY:

13914

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0388

AC:

1300

AN:

33480

American (AMR)

AF:

0.00861

AC:

385

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0644

AC:

1683

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00669

AC:

577

AN:

86258

European-Finnish (FIN)

AF:

0.0118

AC:

632

AN:

53420

Middle Eastern (MID)

AF:

0.0362

AC:

209

AN:

5766

European-Non Finnish (NFE)

AF:

0.0198

AC:

22054

AN:

1111950

Other (OTH)

AF:

0.0213

AC:

1284

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1644

3288

4933

6577

8221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

832

1664

2496

3328

4160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0242

AC:

3690

AN:

152230

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1712

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0361

AC:

1500

AN:

41546

American (AMR)

AF:

0.0128

AC:

196

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0730

AC:

253

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00455

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0121

AC:

128

AN:

10614

Middle Eastern (MID)

AF:

0.0552

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0217

AC:

1477

AN:

68008

Other (OTH)

AF:

0.0237

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

179

358

537

716

895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0248

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.0

(source)

DANN

Benign

0.59

PhyloP100

-0.19

PromoterAI

0.0038

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over