rs1554618420
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_019098.5(CNGB3):c.257del(p.Pro86LeufsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P86P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_019098.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.257del | p.Pro86LeufsTer39 | frameshift_variant | 3/18 | ENST00000320005.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.257del | p.Pro86LeufsTer39 | frameshift_variant | 3/18 | 1 | NM_019098.5 | P1 | |
ENST00000519041.1 | n.448+18620del | intron_variant, non_coding_transcript_variant | 3 | ||||||
CNGB3 | ENST00000519777.1 | n.239del | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
CNGB3 | ENST00000681746.1 | c.257del | p.Pro86LeufsTer39 | frameshift_variant, NMD_transcript_variant | 3/19 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461606Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727126
GnomAD4 genome ? Cov.: 32
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 | Sep 05, 2021 | ClinVar contains an entry for this variant (Variation ID: 427647). This premature translational stop signal has been observed in individual(s) with CNGB3-related conditions (PMID: 28795510). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro86Leufs*39) 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). 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