12-53104205-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003578.4(SOAT2):c.137A>C(p.Glu46Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00022 in 1,599,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

SOAT2
NM_003578.4 missense, splice_region

Scores

Splicing: ADA: 0.9996

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

SOAT2 (HGNC:11178): (sterol O-acyltransferase 2) Summary:This gene is a member of a small family of acyl coenzyme A:cholesterol acyltransferases. The gene encodes a membrane-bound enzyme localized in the endoplasmic reticulum that produces intracellular cholesterol esters from long-chain fatty acyl CoA and cholesterol. The cholesterol esters are then stored as cytoplasmic lipid droplets inside the cell. The enzyme is implicated in cholesterol absorption in the intestine and in the assembly and secretion of apolipoprotein B-containing lipoproteins such as very low density lipoprotein (VLDL). Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2008]

SOAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOAT2	NM_003578.4 link	c.137A>C	p.Glu46Ala	missense_variant, splice_region_variant	Exon 2 of 15	ENST00000301466.8	NP_003569.1	O75908-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SOAT2	ENST00000301466.8 link	c.137A>C	p.Glu46Ala	missense_variant, splice_region_variant	Exon 2 of 15	1	NM_003578.4	ENSP00000301466.3	O75908-1
SOAT2	ENST00000551896.5 link	c.137A>C	p.Glu46Ala	missense_variant, splice_region_variant	Exon 2 of 5	2		ENSP00000450120.1	F8VPE9
SOAT2	ENST00000542365.1 link	n.137A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000442234.1	O75908-4

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00293

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251488

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000227

AC:

328

AN:

1447744

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

195

AN XY:

719896

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000218

GnomAD4 genome

AF:

0.000152

AC:

AN:

151300

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

73920

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00294

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137A>C (p.E46A) alteration is located in exon 2 (coding exon 2) of the SOAT2 gene. This alteration results from a A to C substitution at nucleotide position 137, causing the glutamic acid (E) at amino acid position 46 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

.;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

.;L

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.072

Sift

Uncertain

0.0040

D;T

Sift4G

Uncertain

0.017

D;T

Polyphen

0.38

.;B

Vest4

0.46

MutPred

0.28

Gain of MoRF binding (P = 0.0332);Gain of MoRF binding (P = 0.0332);

MVP

0.65

MPC

0.19

ClinPred

0.21

GERP RS

5.0

Varity_R

0.19

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 17

DS_DL_spliceai

0.37

Position offset: 1

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