Variant chr1-179302781-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003101.6(SOAT1):c.97T>A(p.Ser33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,583,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

SOAT1
NM_003101.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.553

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01725167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOAT1	NM_003101.6 linkuse as main transcript	c.97T>A	p.Ser33Thr	missense_variant	2/16	ENST00000367619.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOAT1	ENST00000367619.8 linkuse as main transcript	c.97T>A	p.Ser33Thr	missense_variant	2/16	1	NM_003101.6	P1	P35610-1
SOAT1	ENST00000540564.5 linkuse as main transcript	c.-19T>A		5_prime_UTR_variant	2/15	1			P35610-2
SOAT1	ENST00000426956.1 linkuse as main transcript	c.97T>A	p.Ser33Thr	missense_variant	2/7	3
SOAT1	ENST00000539888.5 linkuse as main transcript	c.-78+8845T>A		intron_variant		2			P35610-3

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000606

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000957

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

221388

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

120288

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.0000390

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000124

Gnomad SAS exome

AF:

0.000364

Gnomad FIN exome

AF:

0.0000483

Gnomad NFE exome

AF:

0.0000475

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000559

AC:

AN:

1432106

Hom.:

Cov.:

AF XY:

0.0000561

AC XY:

AN XY:

712392

show subpopulations

Gnomad4 AFR exome

AF:

0.000350

Gnomad4 AMR exome

AF:

0.0000846

Gnomad4 ASJ exome

AF:

0.0000409

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.000236

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.0000236

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.000211

AC:

AN:

151638

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.000605

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000957

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000252

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 27, 2023

The c.97T>A (p.S33T) alteration is located in exon 2 (coding exon 1) of the SOAT1 gene. This alteration results from a T to A substitution at nucleotide position 97, causing the serine (S) at amino acid position 33 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.5

DANN

Benign

0.37

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.022

Sift

Benign

0.56

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0030

B;.

Vest4

0.23

MVP

0.11

MPC

0.15

ClinPred

0.0049

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.10

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