NM_000384.3:c.10240G>A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000384.3(APOB):c.10240G>A(p.Val3414Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V3414V) has been classified as Likely benign.
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
Publications
- hypercholesterolemia, autosomal dominant, type BInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
- familial hypobetalipoproteinemia 1Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
- homozygous familial hypercholesterolemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251262 AF XY: 0.00 show subpopulations
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:1
This variant is present in population databases (rs749800586, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 3414 of the APOB protein (p.Val3414Met). This variant has not been reported in the literature in individuals affected with APOB-related conditions. ClinVar contains an entry for this variant (Variation ID: 477787). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APOB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Cardiovascular phenotype Uncertain:1
The p.V3414M variant (also known as c.10240G>A), located in coding exon 26 of the APOB gene, results from a G to A substitution at nucleotide position 10240. The valine at codon 3414 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at