chr12-53103650-T-C

Variant names:

• chr12-53103650-T-C
• rs899171644
• NM_003578.4:c.73T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003578.4(SOAT2):​c.73T>C​(p.Cys25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,533,168 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SOAT2 NM_003578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.392
• Publications: 0 publications found

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]

ACMG classification

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=0.057845026).

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.73T>C	p.Cys25Arg	missense	Exon 1 of 15	NP_003569.1	O75908-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOAT2	ENST00000301466.8	TSL:1 MANE Select	c.73T>C	p.Cys25Arg	missense	Exon 1 of 15	ENSP00000301466.3	O75908-1
	SOAT2	ENST00000869113.1		c.73T>C	p.Cys25Arg	missense	Exon 1 of 15	ENSP00000539172.1
	SOAT2	ENST00000869112.1		c.73T>C	p.Cys25Arg	missense	Exon 1 of 14	ENSP00000539171.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151734 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000156 AC: 2 AN: 128074 AF XY: 0.0000291

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000460

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000159 AC: 22 AN: 1381434 Hom.: 0 Cov.: 31 AF XY: 0.0000161 AC XY: 11 AN XY: 681230

African (AFR) AF: 0.00 AC: 0 AN: 31152

American (AMR) AF: 0.0000303 AC: 1 AN: 33036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35584

South Asian (SAS) AF: 0.00 AC: 0 AN: 77496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.0000177 AC: 19 AN: 1073702

Other (OTH) AF: 0.0000348 AC: 2 AN: 57406

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151734 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74094

African (AFR) AF: 0.00 AC: 0 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67844

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.0000376 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.4
DANN	Benign	0.41
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.39
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.014
Sift	Benign	0.068	T
Sift4G	Benign	0.18	T
Polyphen		0.012	B
Vest4		0.024
MVP		0.18
MPC		0.23
ClinPred		0.12	T
GERP RS		-3.5
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.35
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs899171644; hg19: chr12-53497434;