12-53105173-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003578.4(SOAT2):​c.205C>T​(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,589,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R69G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SOAT2
NM_003578.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028392315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOAT2NM_003578.4 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 15 ENST00000301466.8 NP_003569.1 O75908-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOAT2ENST00000301466.8 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 15 1 NM_003578.4 ENSP00000301466.3 O75908-1
SOAT2ENST00000551896.5 linkc.205C>T p.Arg69Trp missense_variant Exon 3 of 5 2 ENSP00000450120.1 F8VPE9
SOAT2ENST00000542365.1 linkn.205C>T non_coding_transcript_exon_variant Exon 3 of 14 2 ENSP00000442234.1 O75908-4

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152038
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000142
AC:
3
AN:
211732
Hom.:
0
AF XY:
0.00000880
AC XY:
1
AN XY:
113680
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000644
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000215
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000216
AC:
31
AN:
1437248
Hom.:
0
Cov.:
32
AF XY:
0.0000154
AC XY:
11
AN XY:
712754
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000785
Gnomad4 SAS exome
AF:
0.0000364
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000200
Gnomad4 OTH exome
AF:
0.0000336
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152038
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000412
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Benign
0.69
DEOGEN2
Benign
0.24
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0036
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.028
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.8
.;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.039
Sift
Benign
0.15
T;D
Sift4G
Benign
0.20
T;T
Polyphen
0.0
.;B
Vest4
0.12
MutPred
0.31
Loss of MoRF binding (P = 0.0668);Loss of MoRF binding (P = 0.0668);
MVP
0.25
MPC
0.13
ClinPred
0.065
T
GERP RS
-0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.062
gMVP
0.32

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.

Other links and lift over

dbSNP: rs746145311; hg19: chr12-53498957; API