chr19-11106638-C-A
Variant summary
Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PS1PM1PM2PM5PP3_StrongPP5
The ENST00000558518.6(LDLR):c.768C>A(p.Asp256Glu) 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 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D256G) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000558518.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.768C>A | p.Asp256Glu | missense_variant | 5/18 | ENST00000558518.6 | NP_000518.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.768C>A | p.Asp256Glu | missense_variant | 5/18 | 1 | NM_000527.5 | ENSP00000454071 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727242
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | curation;literature only | Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge | Mar 01, 2016 | - - |
Familial hypercholesterolemia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Laboratory of Molecular Genetics, National Medical Research Center for Therapy and Preventive Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at