rs866395428
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001122769.3(LCA5):c.838C>T(p.Arg280Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R280R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001122769.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCA5 | NM_001122769.3 | c.838C>T | p.Arg280Ter | stop_gained | 4/8 | ENST00000369846.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCA5 | ENST00000369846.9 | c.838C>T | p.Arg280Ter | stop_gained | 4/8 | 1 | NM_001122769.3 | P1 | |
LCA5 | ENST00000392959.5 | c.838C>T | p.Arg280Ter | stop_gained | 5/9 | 1 | P1 | ||
ENST00000652956.1 | n.469+12193G>A | intron_variant, non_coding_transcript_variant | |||||||
LCA5 | ENST00000467898.3 | c.838C>T | p.Arg280Ter | stop_gained | 4/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460954Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726828
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Leber congenital amaurosis 5 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 26, 2023 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 12, 2021 | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 18, 2016 | - - |
Leber congenital amaurosis Pathogenic:1
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | This sequence change creates a premature translational stop signal (p.Arg280*) in the LCA5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LCA5 are known to be pathogenic (PMID: 17546029, 23946133). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with LCA5-related conditions (PMID: 8571951, 28041643). ClinVar contains an entry for this variant (Variation ID: 438153). For these reasons, this variant has been classified as Pathogenic. - |
Retinal dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at