dbSNP rs753091495: SOAT2:p.Ala56Glu (chr12-53105135-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003578.4(SOAT2):c.167C>A(p.Ala56Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 1,413,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A56P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SOAT2
NM_003578.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0390

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.015717834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003578.4. 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
	SOAT2	NM_003578.4	MANE Select	c.167C>A	p.Ala56Glu	missense	Exon 3 of 15	NP_003569.1	O75908-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOAT2	ENST00000301466.8	TSL:1 MANE Select	c.167C>A	p.Ala56Glu	missense	Exon 3 of 15	ENSP00000301466.3	O75908-1
SOAT2	ENST00000869113.1		c.167C>A	p.Ala56Glu	missense	Exon 3 of 15	ENSP00000539172.1
SOAT2	ENST00000869112.1		c.167C>A	p.Ala56Glu	missense	Exon 3 of 14	ENSP00000539171.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000565

AC:

AN:

176982

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000604

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000566

AC:

AN:

1413674

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

698746

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32188

American (AMR)

AF:

0.00

AC:

AN:

37358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25292

East Asian (EAS)

AF:

0.00

AC:

AN:

36812

South Asian (SAS)

AF:

0.00

AC:

AN:

80168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000736

AC:

AN:

1087104

Other (OTH)

AF:

0.00

AC:

AN:

58640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000833

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.26

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.64

M_CAP

Benign

0.011

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

0.039

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.11

Sift

Benign

0.040

Sift4G

Pathogenic

0.0

Polyphen

0.81

Vest4

0.31

MutPred

0.39

Loss of MoRF binding (P = 0.0405)

MVP

0.36

MPC

0.47

ClinPred

0.29

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.75

Mutation Taster

=90/10

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over