rs371318766
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_019098.5(CNGB3):āc.756C>Gā(p.Tyr252Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,920 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 (ā ). 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNGB3 | NM_019098.5 | c.756C>G | p.Tyr252Ter | stop_gained | 6/18 | ENST00000320005.6 | |
CNGB3 | XM_011517138.3 | c.342C>G | p.Tyr114Ter | stop_gained | 4/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.756C>G | p.Tyr252Ter | stop_gained | 6/18 | 1 | NM_019098.5 | P1 | |
CNGB3 | ENST00000681746.1 | c.756C>G | p.Tyr252Ter | stop_gained, NMD_transcript_variant | 6/19 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251446Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727164
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
Achromatopsia 3 Pathogenic:1
Pathogenic, no assertion criteria provided | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Mar 27, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2023 | This sequence change creates a premature translational stop signal (p.Tyr252*) 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 (rs371318766, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of achromatopsia (PMID: 28795510). ClinVar contains an entry for this variant (Variation ID: 427685). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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