Variant 1-179342121-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_003101.6(SOAT1):c.788T>C(p.Phe263Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SOAT1
NM_003101.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a mutagenesis_site Strongly reduced cholesterol O-acyltransferase activity. (size 0) in uniprot entity SOAT1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6 linkuse as main transcript	c.788T>C	p.Phe263Ser	missense_variant	8/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8 linkuse as main transcript	c.788T>C	p.Phe263Ser	missense_variant	8/16	1	NM_003101.6	P1	P35610-1
SOAT1	ENST00000540564.5 linkuse as main transcript	c.614T>C	p.Phe205Ser	missense_variant	7/15	1			P35610-2
SOAT1	ENST00000539888.5 linkuse as main transcript	c.593T>C	p.Phe198Ser	missense_variant	7/15	2			P35610-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461514

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.788T>C (p.F263S) alteration is located in exon 8 (coding exon 7) of the SOAT1 gene. This alteration results from a T to C substitution at nucleotide position 788, causing the phenylalanine (F) at amino acid position 263 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

Pathogenic

0.67

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.90

.;.;D

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

.;.;M

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.73

.;.;P

Vest4

0.74

MutPred

0.83

.;.;Loss of stability (P = 0.0218);

MVP

0.36

MPC

0.41

ClinPred

0.93

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.79

gMVP

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over