rs786204762
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_019098.5(CNGB3):c.1119G>A(p.Trp373Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,412 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 Likely pathogenic (★★). 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.1119G>A | p.Trp373Ter | stop_gained | 10/18 | ENST00000320005.6 | |
CNGB3 | XM_011517138.3 | c.705G>A | p.Trp235Ter | stop_gained | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.1119G>A | p.Trp373Ter | stop_gained | 10/18 | 1 | NM_019098.5 | P1 | |
CNGB3 | ENST00000681546.1 | n.939G>A | non_coding_transcript_exon_variant | 5/13 | |||||
CNGB3 | ENST00000681746.1 | c.1119G>A | p.Trp373Ter | stop_gained, NMD_transcript_variant | 10/19 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1457412Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3AN XY: 725080
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Achromatopsia 3 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | literature only | Counsyl | Feb 23, 2015 | - - |
Pathogenic, no assertion criteria provided | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Mar 27, 2017 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189190). This premature translational stop signal has been observed in individual(s) with achromatopsia (PMID: 15657609, 28795510). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp373*) 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). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2016 | The W373X pathogenic variant in the CNGB3 gene has been reported previously in the homozygous state in an individual with achromatopsia (Kohl et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W373X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, we interpret W373X as a pathogenic variant. - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Aug 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at