1-179347606-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003101.6(SOAT1):āc.1124T>Cā(p.Leu375Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SOAT1
NM_003101.6 missense
NM_003101.6 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.92
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOAT1 | NM_003101.6 | c.1124T>C | p.Leu375Pro | missense_variant | 12/16 | ENST00000367619.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOAT1 | ENST00000367619.8 | c.1124T>C | p.Leu375Pro | missense_variant | 12/16 | 1 | NM_003101.6 | P1 | |
SOAT1 | ENST00000540564.5 | c.950T>C | p.Leu317Pro | missense_variant | 11/15 | 1 | |||
SOAT1 | ENST00000539888.5 | c.929T>C | p.Leu310Pro | missense_variant | 11/15 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1452034Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 723072
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1452034
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
723072
Gnomad4 AFR exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Jan 04, 2024 | The c.1124T>C (p.L375P) alteration is located in exon 12 (coding exon 11) of the SOAT1 gene. This alteration results from a T to C substitution at nucleotide position 1124, causing the leucine (L) at amino acid position 375 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;.;D
Vest4
MutPred
0.68
.;.;Loss of catalytic residue at L375 (P = 0.0366);
MVP
MPC
0.88
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.