1-179335639-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003101.6(SOAT1):c.311A>G(p.Lys104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SOAT1 NM_003101.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16254121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6	c.311A>G	p.Lys104Arg	missense_variant	4/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8	c.311A>G	p.Lys104Arg	missense_variant	4/16	1	NM_003101.6	P1
SOAT1	ENST00000540564.5	c.137A>G	p.Lys46Arg	missense_variant	3/15	1
SOAT1	ENST00000539888.5	c.116A>G	p.Lys39Arg	missense_variant	3/15	2
SOAT1	ENST00000426956.1	c.311A>G	p.Lys104Arg	missense_variant	4/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460898 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.311A>G (p.K104R) alteration is located in exon 4 (coding exon 3) of the SOAT1 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the lysine (K) at amino acid position 104 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	18
Dann	Uncertain	1.0
Eigen	Benign	-0.071
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.036	D;T;T;D
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.011	.;.;B;.
Vest4		0.18
MutPred		0.31		.;.;Loss of ubiquitination at K104 (P = 0.0047);Loss of ubiquitination at K104 (P = 0.0047);
MVP		0.29
MPC		0.13
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-179304774;