chr11-116830806-G-GCTTCAT
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4
The NM_000040.3(APOC3):c.90_95dup(p.Phe31_Met32insIlePhe) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
APOC3
NM_000040.3 inframe_insertion
NM_000040.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.393
Genes affected
APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_000040.3.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOC3 | NM_000040.3 | c.90_95dup | p.Phe31_Met32insIlePhe | inframe_insertion | 3/4 | ENST00000227667.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOC3 | ENST00000227667.8 | c.90_95dup | p.Phe31_Met32insIlePhe | inframe_insertion | 3/4 | 1 | NM_000040.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461012Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 726800
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
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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 | Mar 02, 2022 | The c.90_95dupCTTCAT variant (also known as p.F31_M32insIF), located in coding exon 2 of the APOC3 gene, results from an in-frame duplication of CTTCAT at nucleotide positions 90 to 95. This results in the insertion of 2 extra residues (isoleucine and phenylalanine) between codons 31 and 32. This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at