chr1-179341281-G-T

Position:

• chr1-179341281-G-T

Variant summary

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

The NM_003101.6(SOAT1):​c.751G>T​(p.Ala251Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOAT1 NM_003101.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

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]

SOAT1 (HGNC:):

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	Protein	UniProt
SOAT1	NM_003101.6	c.751G>T	p.Ala251Ser	missense_variant	7/16	ENST00000367619.8	NP_003092.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOAT1	ENST00000367619.8	c.751G>T	p.Ala251Ser	missense_variant	7/16	1	NM_003101.6	ENSP00000356591.3
SOAT1	ENST00000540564.5	c.577G>T	p.Ala193Ser	missense_variant	6/15	1		ENSP00000445315.1
SOAT1	ENST00000539888.5	c.556G>T	p.Ala186Ser	missense_variant	6/15	2		ENSP00000441356.1
SOAT1	ENST00000426956.1	c.751G>T	p.Ala251Ser	missense_variant	7/7	3		ENSP00000411309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 19, 2024

The c.751G>T (p.A251S) alteration is located in exon 7 (coding exon 6) of the SOAT1 gene. This alteration results from a G to T substitution at nucleotide position 751, causing the alanine (A) at amino acid position 251 to be replaced by a serine (S). 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	0.29
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	.;.;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.7	.;.;H;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.57
MutPred		0.67		.;.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.63
MPC		0.63
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-179310416;