chr12-53103642-G-A

Position:

chr12-53103642-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003578.4(SOAT2):c.65G>A(p.Arg22His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,539,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SOAT2
NM_003578.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.339

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0032445788).

BP6

Variant 12-53103642-G-A is Benign according to our data. Variant chr12-53103642-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3321368.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOAT2	NM_003578.4 linkuse as main transcript	c.65G>A	p.Arg22His	missense_variant	1/15	ENST00000301466.8	NP_003569.1	O75908-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOAT2	ENST00000301466.8 linkuse as main transcript	c.65G>A	p.Arg22His	missense_variant	1/15	1	NM_003578.4	ENSP00000301466.3	O75908-1
SOAT2	ENST00000551896.5 linkuse as main transcript	c.65G>A	p.Arg22His	missense_variant	1/5	2		ENSP00000450120.1	F8VPE9
SOAT2	ENST00000542365.1 linkuse as main transcript	n.65G>A		non_coding_transcript_exon_variant	1/14	2		ENSP00000442234.1	O75908-4

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

133222

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

71194

show subpopulations

Gnomad AFR exome

AF:

0.00293

Gnomad AMR exome

AF:

0.0000431

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000830

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

162

AN:

1387192

Hom.:

Cov.:

AF XY:

0.0000994

AC XY:

AN XY:

684194

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000771

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152264

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000390

Hom.:

Bravo

AF:

0.000790

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.000429

AC:

ExAC

AF:

0.000264

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.5

DANN

Benign

0.79

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.015

Sift

Benign

0.31

T;T

Sift4G

Benign

0.087

T;T

Polyphen

0.0

.;B

Vest4

0.049

MVP

0.099

MPC

0.16

ClinPred

0.020

GERP RS

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.24

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

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