rs1052078370
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_019098.5(CNGB3):c.208C>T(p.Gln70*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,406,450 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 (★★). 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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.208C>T | p.Gln70* | stop_gained | 2/18 | 1 | NM_019098.5 | ENSP00000316605.5 | ||
CNGB3 | ENST00000519777.1 | n.190C>T | non_coding_transcript_exon_variant | 2/4 | 2 | |||||
CNGB3 | ENST00000681746.1 | n.208C>T | non_coding_transcript_exon_variant | 2/19 | ENSP00000505959.1 | |||||
ENSG00000254115 | ENST00000519041.1 | n.449-21178G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 exomes AF: 0.00000421 AC: 1AN: 237748Hom.: 0 AF XY: 0.00000776 AC XY: 1AN XY: 128838
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1406450Hom.: 0 Cov.: 40 AF XY: 0.00000286 AC XY: 2AN XY: 699764
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Achromatopsia 3 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Mar 27, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 15, 2024 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 07, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 427681). This premature translational stop signal has been observed in individual(s) with achromatopsia (PMID: 28795510). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln70*) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at