2-98370042-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001298.3(CNGA3):c.67C>T(p.Arg23*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,826 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 (★★).
Frequency
Consequence
NM_001298.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251056Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135700
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461704Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727124
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
Achromatopsia 2 Pathogenic:3
- -
The CNGA3 c.67C>T (p.Arg23Ter) stop-gained variant was reported in at least five individuals with achromatopsia or another cone dystrophy, including two homozygotes and three compound heterozygotes, and in two unaffected heterozygous parents of individuals (Johnson et al. 2004; Koeppen et al. 2008; Sundaram et al. 2014; Aboshiha et al. 2014; Zelinger et al. 2015; Huang et al. 2016). The variant was absent from six control individuals and from 100 control chromosomes. The variant is reported at a frequency of 0.00012 in the East Asian population of the Exome Aggregation Consortium, but this is based on only one allele in a region of good sequence coverage so it is presumed to be rare. Based on the evidence and due to the potential impact of stop-gained variants, the p.Arg23Ter variant is classified as pathogenic for achromatopsia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
- -
Achromatopsia Pathogenic:1
- -
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Arg23*) in the CNGA3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGA3 are known to be pathogenic (PMID: 14757870, 24903488, 25637600). This variant is present in population databases (rs777509481, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with CNGA3-related conditions (PMID: 14757870, 30682209). ClinVar contains an entry for this variant (Variation ID: 337652). 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