rs879254869
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_000527.5(LDLR):āc.1339T>Cā(p.Ser447Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,690 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 Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S447C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000527.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LDLR | NM_000527.5 | c.1339T>C | p.Ser447Pro | missense_variant | 9/18 | ENST00000558518.6 | |
MIR6886 | NR_106946.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDLR | ENST00000558518.6 | c.1339T>C | p.Ser447Pro | missense_variant | 9/18 | 1 | NM_000527.5 | P3 | |
MIR6886 | ENST00000619864.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461690Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727146
GnomAD4 genome ? Cov.: 29
ClinVar
Submissions by phenotype
Hypercholesterolemia, familial, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | literature only | LDLR-LOVD, British Heart Foundation | Mar 25, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at