rs786205644
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004744.5(LRAT):c.233_242del(p.Leu78ArgfsTer85) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
LRAT
NM_004744.5 frameshift
NM_004744.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.95
Genes affected
LRAT (HGNC:6685): (lecithin retinol acyltransferase) The protein encoded by this gene localizes to the endoplasmic reticulum, where it catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester. This reaction is an important step in vitamin A metabolism in the visual system. Mutations in this gene have been associated with early-onset severe retinal dystrophy and Leber congenital amaurosis 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-154744558-CTGTTGGCCCT-C is Pathogenic according to our data. Variant chr4-154744558-CTGTTGGCCCT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191324.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-154744558-CTGTTGGCCCT-C is described in Lovd as [Likely_pathogenic]. Variant chr4-154744558-CTGTTGGCCCT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRAT | NM_004744.5 | c.233_242del | p.Leu78ArgfsTer85 | frameshift_variant | 2/3 | ENST00000336356.4 | |
LRAT | NM_001301645.2 | c.233_242del | p.Leu78ArgfsTer85 | frameshift_variant | 2/3 | ||
LRAT | XM_047416405.1 | c.233_242del | p.Leu78ArgfsTer85 | frameshift_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRAT | ENST00000336356.4 | c.233_242del | p.Leu78ArgfsTer85 | frameshift_variant | 2/3 | 1 | NM_004744.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive retinitis pigmentosa Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Faculty of Health Sciences, Beirut Arab University | Sep 10, 2015 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at