11-116835821-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000039.3(APOA1):āc.791T>Cā(p.Leu264Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,730 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
APOA1
NM_000039.3 missense
NM_000039.3 missense
Scores
4
13
2
Clinical Significance
Conservation
PhyloP100: 3.94
Genes affected
APOA1 (HGNC:600): (apolipoprotein A1) This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
APOA1 | NM_000039.3 | c.791T>C | p.Leu264Pro | missense_variant | 4/4 | ENST00000236850.5 | NP_000030.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460730Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726684
GnomAD4 exome
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2
AN:
1460730
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32
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1
AN XY:
726684
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 11, 2024 | The p.L264P variant (also known as c.791T>C), located in coding exon 3 of the APOA1 gene, results from a T to C substitution at nucleotide position 791. The leucine at codon 264 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T;.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;.;D;D
Vest4
MutPred
Gain of disorder (P = 0.0336);Gain of disorder (P = 0.0336);.;Gain of disorder (P = 0.0336);Gain of disorder (P = 0.0336);
MVP
MPC
2.0
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.