rs200805087
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_019098.5(CNGB3):c.1810C>T(p.Arg604Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,094 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. R604R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_019098.5 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 |
---|---|---|---|---|---|---|---|
CNGB3 | NM_019098.5 | c.1810C>T | p.Arg604Ter | stop_gained | 16/18 | ENST00000320005.6 | |
CNGB3 | XM_011517138.3 | c.1396C>T | p.Arg466Ter | stop_gained | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.1810C>T | p.Arg604Ter | stop_gained | 16/18 | 1 | NM_019098.5 | P1 | |
CNGB3 | ENST00000681546.1 | n.1630C>T | non_coding_transcript_exon_variant | 11/13 | |||||
CNGB3 | ENST00000681746.1 | c.*221C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/19 | |||||
CNGB3 | ENST00000517327.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250986Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727214
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74462
ClinVar
Submissions by phenotype
Achromatopsia Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 09, 2021 | - - |
Abnormality of the eye Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | Undetermined rare ocular disorder with frequency of less than eight patients - |
Achromatopsia 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change creates a premature translational stop signal (p.Arg604*) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). This variant is present in population databases (rs200805087, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CNGB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 438042). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at