12-53103654-G-C

Variant names:

• chr12-53103654-G-C
• rs1308804464
• NM_003578.4:c.77G>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.77G>C​(p.Gly26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,814 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. G26E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SOAT2 NM_003578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• 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=0.04960096).

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.77G>C	p.Gly26Ala	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.77G>C	p.Gly26Ala	missense	Exon 1 of 15	ENSP00000301466.3	O75908-1
	SOAT2	ENST00000869113.1		c.77G>C	p.Gly26Ala	missense	Exon 1 of 15	ENSP00000539172.1
	SOAT2	ENST00000869112.1		c.77G>C	p.Gly26Ala	missense	Exon 1 of 14	ENSP00000539171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380814 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 680882

African (AFR) AF: 0.00 AC: 0 AN: 31192

American (AMR) AF: 0.00 AC: 0 AN: 33262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24082

East Asian (EAS) AF: 0.00 AC: 0 AN: 35618

South Asian (SAS) AF: 0.00 AC: 0 AN: 77398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1073378

Other (OTH) AF: 0.00 AC: 0 AN: 57392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.3
DANN	Benign	0.72
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.010
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.031
Sift	Benign	0.21	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.088
MutPred		0.095		Gain of helix (P = 0.0893)
MVP		0.44
MPC		0.14
ClinPred		0.15	T
GERP RS		1.8
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.32
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1308804464; hg19: chr12-53497438;