rs1382988295
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PS1PM1PM2PM5PP5_Very_Strong
The NM_000384.3(APOB):c.10182G>T(p.Lys3394Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K3394T) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.10182G>T | p.Lys3394Asn | missense_variant | 26/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.10182G>T | p.Lys3394Asn | missense_variant | 26/29 | 1 | NM_000384.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461762Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727180
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2020 | For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt APOB protein function. This variant has been observed to segregate with familial hypercholesterolemia in a family (PMID: 22408029). ClinVar contains an entry for this variant (Variation ID: 438310). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 3394 of the APOB protein (p.Lys3394Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 07, 2021 | - - |
Hypercholesterolemia, familial, 1 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum | - | - - |
Likely pathogenic, criteria provided, single submitter | curation;literature only | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at