rs398122836
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_002337.4(LRPAP1):c.863_864del(p.Ile288ArgfsTer118) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 35)
Consequence
LRPAP1
NM_002337.4 frameshift
NM_002337.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.54
Genes affected
LRPAP1 (HGNC:6701): (LDL receptor related protein associated protein 1) This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.196 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-3514898-CGA-C is Pathogenic according to our data. Variant chr4-3514898-CGA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 65461.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRPAP1 | NM_002337.4 | c.863_864del | p.Ile288ArgfsTer118 | frameshift_variant | 7/8 | ENST00000650182.1 | |
LRPAP1 | NR_110005.2 | n.826_827del | non_coding_transcript_exon_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRPAP1 | ENST00000650182.1 | c.863_864del | p.Ile288ArgfsTer118 | frameshift_variant | 7/8 | NM_002337.4 | P1 | ||
LRPAP1 | ENST00000296325.9 | n.826_827del | non_coding_transcript_exon_variant | 7/8 | 1 | ||||
LRPAP1 | ENST00000648517.1 | c.*355_*356del | 3_prime_UTR_variant, NMD_transcript_variant | 8/8 |
Frequencies
GnomAD3 genomes ? Cov.: 35
GnomAD3 genomes
?
Cov.:
35
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 35
GnomAD4 genome
?
Cov.:
35
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Myopia 23, autosomal recessive Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 08, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at