1-179351443-A-T

Position:

• chr1-179351443-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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. Q526R) has been classified as Likely benign.

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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6	c.1577A>T	p.Gln526Leu	missense_variant	15/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8	c.1577A>T	p.Gln526Leu	missense_variant	15/16	1	NM_003101.6	P1
SOAT1	ENST00000540564.5	c.1403A>T	p.Gln468Leu	missense_variant	14/15	1
SOAT1	ENST00000539888.5	c.1382A>T	p.Gln461Leu	missense_variant	14/15	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-0.046
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.013	P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.21	T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306731; hg19: chr1-179320578;