rs786205653
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001122769.3(LCA5):c.1020del(p.Lys340AsnfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. K340K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LCA5
NM_001122769.3 frameshift
NM_001122769.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.164
Genes affected
LCA5 (HGNC:31923): (lebercilin LCA5) This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]
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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 6-79491665-GC-G is Pathogenic according to our data. Variant chr6-79491665-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-79491665-GC-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCA5 | NM_001122769.3 | c.1020del | p.Lys340AsnfsTer7 | frameshift_variant | 6/8 | ENST00000369846.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCA5 | ENST00000369846.9 | c.1020del | p.Lys340AsnfsTer7 | frameshift_variant | 6/8 | 1 | NM_001122769.3 | P1 | |
LCA5 | ENST00000392959.5 | c.1020del | p.Lys340AsnfsTer7 | frameshift_variant | 7/9 | 1 | P1 | ||
ENST00000652956.1 | n.469+10226del | intron_variant, non_coding_transcript_variant | |||||||
LCA5 | ENST00000467898.3 | c.1020del | p.Lys340AsnfsTer7 | frameshift_variant | 6/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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
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