rs794726662
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_000229.2(LCAT):c.493_494insGCG(p.Arg164_Ala165insGly) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A165A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
LCAT
NM_000229.2 inframe_insertion
NM_000229.2 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.08
Genes affected
LCAT (HGNC:6522): (lecithin-cholesterol acyltransferase) This gene encodes the extracellular cholesterol esterifying enzyme, lecithin-cholesterol acyltransferase. The esterification of cholesterol is required for cholesterol transport. Mutations in this gene have been found to cause fish-eye disease as well as LCAT deficiency. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_000229.2
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000229.2. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 16-67942700-G-GCGC is Pathogenic according to our data. Variant chr16-67942700-G-GCGC is described in ClinVar as [Pathogenic]. Clinvar id is 3658.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCAT | NM_000229.2 | c.493_494insGCG | p.Arg164_Ala165insGly | inframe_insertion | 4/6 | ENST00000264005.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCAT | ENST00000264005.10 | c.493_494insGCG | p.Arg164_Ala165insGly | inframe_insertion | 4/6 | 1 | NM_000229.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
LCAT deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 28, 1991 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at