rs1554604552
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_019098.5(CNGB3):c.2221del(p.Asp741IlefsTer88) 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CNGB3
NM_019098.5 frameshift
NM_019098.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0310
Genes affected
CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.086 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNGB3 | NM_019098.5 | c.2221del | p.Asp741IlefsTer88 | frameshift_variant | 18/18 | ENST00000320005.6 | |
CNGB3 | XM_011517138.3 | c.1807del | p.Asp603IlefsTer88 | frameshift_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.2221del | p.Asp741IlefsTer88 | frameshift_variant | 18/18 | 1 | NM_019098.5 | P1 | |
CNGB3 | ENST00000517327.5 | c.276+2676del | intron_variant | 3 | |||||
CNGB3 | ENST00000681546.1 | n.2041del | non_coding_transcript_exon_variant | 13/13 | |||||
CNGB3 | ENST00000681746.1 | c.*632del | 3_prime_UTR_variant, NMD_transcript_variant | 19/19 |
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: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2021 | This sequence change results in a frameshift in the CNGB3 gene (p.Asp741Ilefs*88). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the CNGB3 protein and extend the protein by 18 additional amino acid residues. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant results in an extension of the CNGB3 protein. Other variant(s) that result in a similarly extended protein product (p.Ser787Alafs*42) have been observed in individuals with CNGB3-related disease (PMID: 28795510). This suggests that these extensions may be clinically significant. ClinVar contains an entry for this variant (Variation ID: 427667). This frameshift has been observed in individual(s) with achromatopsia (PMID: 28795510). This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at