1-179351443-A-T

Variant names:

• chr1-179351443-A-T
• rs13306731
• NM_003101.6:c.1577A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003101.6(SOAT1):​c.1577A>T​(p.Gln526Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SOAT1 NM_003101.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 34 publications found

Genes affected

SOAT1 (HGNC:11177): (sterol O-acyltransferase 1) The protein encoded by this gene belongs to the acyltransferase family. It is located in the endoplasmic reticulum, and catalyzes the formation of fatty acid-cholesterol esters. This gene has been implicated in the formation of beta-amyloid and atherosclerotic plaques by controlling the equilibrium between free cholesterol and cytoplasmic cholesteryl esters. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003101.6. 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
	SOAT1	NM_003101.6	MANE Select	c.1577A>T	p.Gln526Leu	missense	Exon 15 of 16	NP_003092.4
	SOAT1	NM_001252511.2		c.1403A>T	p.Gln468Leu	missense	Exon 14 of 15	NP_001239440.1	P35610-2
	SOAT1	NM_001252512.2		c.1382A>T	p.Gln461Leu	missense	Exon 14 of 15	NP_001239441.1	P35610-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOAT1	ENST00000367619.8	TSL:1 MANE Select	c.1577A>T	p.Gln526Leu	missense	Exon 15 of 16	ENSP00000356591.3	P35610-1
	SOAT1	ENST00000540564.5	TSL:1	c.1403A>T	p.Gln468Leu	missense	Exon 14 of 15	ENSP00000445315.1	P35610-2
	SOAT1	ENST00000904814.1		c.1604A>T	p.Gln535Leu	missense	Exon 15 of 16	ENSP00000574873.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.029	B
Vest4		0.48
MutPred		0.40		Loss of methylation at K531 (P = 0.0803)
MVP		0.33
MPC		0.27
ClinPred		0.55	D
GERP RS		5.6
Varity_R		0.099
gMVP		0.76
Mutation Taster		=57/43	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: rs13306731; hg19: chr1-179320578;