rs753791521
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021147.5(CCNO):c.845T>C(p.Leu282Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,274 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. L282L) has been classified as Likely benign.
Frequency
Consequence
NM_021147.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCNO | NM_021147.5 | c.845T>C | p.Leu282Pro | missense_variant | 3/3 | ENST00000282572.5 | |
CCNO | NR_125346.2 | n.1306T>C | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125347.2 | n.935T>C | non_coding_transcript_exon_variant | 3/3 | |||
CCNO | NR_125348.1 | n.909T>C | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCNO | ENST00000282572.5 | c.845T>C | p.Leu282Pro | missense_variant | 3/3 | 1 | NM_021147.5 | P1 | |
CCNO | ENST00000501463.2 | c.*825T>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249362Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135250
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461076Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726876
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74362
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 282 of the CCNO protein (p.Leu282Pro). This variant is present in population databases (rs753791521, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CCNO-related conditions. ClinVar contains an entry for this variant (Variation ID: 454919). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CCNO 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