rs35574083
- chr1-55039879-ACTGCTGCTG-A
- chr1-55039879-ACTGCTGCTG-ACTG
- chr1-55039879-ACTGCTGCTG-ACTGCTG
- chr1-55039879-ACTGCTGCTG-ACTGCTGCTGCTG
- chr1-55039879-ACTGCTGCTG-ACTGCTGCTGCTGCTG
- chr1-55039879-ACTGCTGCTG-ACTGCTGCTGCTGCTGCTG
- chr1-55039879-ACTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTG
- chr1-55039879-ACTGCTGCTG-ACTGCTGCTGCTGCTGCTGCTGCTG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_174936.4(PCSK9):βc.57_65delβ(p.Leu21_Leu23del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,557,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. L15L) has been classified as Likely benign.
Frequency
Consequence
NM_174936.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK9 | NM_174936.4 | c.57_65del | p.Leu21_Leu23del | inframe_deletion | 1/12 | ENST00000302118.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK9 | ENST00000302118.5 | c.57_65del | p.Leu21_Leu23del | inframe_deletion | 1/12 | 1 | NM_174936.4 | P2 | |
PCSK9 | ENST00000710286.1 | c.414_422del | p.Leu140_Leu142del | inframe_deletion | 1/12 | A2 | |||
PCSK9 | ENST00000673726.1 | c.57_65del | p.Leu21_Leu23del | inframe_deletion, NMD_transcript_variant | 1/6 | ||||
PCSK9 | ENST00000673913.2 | c.57_65del | p.Leu21_Leu23del | inframe_deletion, NMD_transcript_variant | 1/12 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152070Hom.: 0 Cov.: 31
GnomAD4 exome AF: 7.11e-7 AC: 1AN: 1405754Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 694300
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152070Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74294
ClinVar
Submissions by phenotype
Familial hypercholesterolemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 30, 2018 | Variant of Uncertain Significance due to insufficient evidence: This variant is an in-frame deletion of three amino acids in a poorly conserved region of the signal peptide of the PCSK9 protein. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with familial hypercholesterolemia in the literature. Computational splicing tools suggest that this variant may not impact RNA splicing. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at