chr12-53105935-A-G

Variant names:

• chr12-53105935-A-G
• rs961805403
• NM_003578.4:c.364A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_003578.4(SOAT2):​c.364A>G​(p.Thr122Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,557,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00010 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SOAT2 NM_003578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.23
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

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.364A>G	p.Thr122Ala	missense	Exon 5 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.364A>G	p.Thr122Ala	missense	Exon 5 of 15	ENSP00000301466.3	O75908-1
	SOAT2	ENST00000869113.1		c.364A>G	p.Thr122Ala	missense	Exon 5 of 15	ENSP00000539172.1
	SOAT2	ENST00000869112.1		c.364A>G	p.Thr122Ala	missense	Exon 5 of 14	ENSP00000539171.1

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 12 AN: 118132 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000973

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: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1438938 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 715808

African (AFR) AF: 0.00 AC: 0 AN: 31672

American (AMR) AF: 0.0000455 AC: 2 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100154

Other (OTH) AF: 0.0000170 AC: 1 AN: 58882

GnomAD4 genome AF: 0.000102 AC: 12 AN: 118132 Hom.: 1 Cov.: 31 AF XY: 0.0000867 AC XY: 5 AN XY: 57670

African (AFR) AF: 0.00 AC: 0 AN: 24752

American (AMR) AF: 0.000973 AC: 12 AN: 12336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2856

East Asian (EAS) AF: 0.00 AC: 0 AN: 3860

South Asian (SAS) AF: 0.00 AC: 0 AN: 4232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58966

Other (OTH) AF: 0.00 AC: 0 AN: 1674

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000159

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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		9.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.74		Loss of stability (P = 0.1361)
MVP		0.64
MPC		0.58
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.89
Mutation Taster		=24/76	disease causing

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

Other links and lift over

dbSNP: rs961805403; hg19: chr12-53499719;