chr8-86632879-T-C
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_019098.5(CNGB3):c.1193A>G(p.Tyr398Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,612,416 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y398Y) has been classified as Likely benign.
Frequency
Consequence
NM_019098.5 missense
Scores
Clinical Significance
Conservation
Publications
- achromatopsia 3Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
- CNGB3-related retinopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- cone dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- achromatopsiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- severe early-childhood-onset retinal dystrophyInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.1193A>G | p.Tyr398Cys | missense_variant | Exon 11 of 18 | 1 | NM_019098.5 | ENSP00000316605.5 | ||
CNGB3 | ENST00000681546.1 | n.1013A>G | non_coding_transcript_exon_variant | Exon 6 of 13 | ||||||
CNGB3 | ENST00000681746.1 | n.1193A>G | non_coding_transcript_exon_variant | Exon 11 of 19 | ENSP00000505959.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000478 AC: 12AN: 250880 AF XY: 0.0000516 show subpopulations
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460106Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 726378 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Achromatopsia Uncertain:1
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not provided Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 398 of the CNGB3 protein (p.Tyr398Cys). This variant is present in population databases (rs564759960, gnomAD 0.04%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 25326637). ClinVar contains an entry for this variant (Variation ID: 242507). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CNGB3 protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at