rs373501045
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001364171.2(ODAD1):c.1186C>T(p.Arg396Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,613,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R396H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001364171.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD1 | NM_001364171.2 | c.1186C>T | p.Arg396Cys | missense_variant | 12/16 | ENST00000674294.1 | |
ODAD1 | NM_144577.4 | c.1075C>T | p.Arg359Cys | missense_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD1 | ENST00000674294.1 | c.1186C>T | p.Arg396Cys | missense_variant | 12/16 | NM_001364171.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249416Hom.: 0 AF XY: 0.0000741 AC XY: 10AN XY: 135040
GnomAD4 exome AF: 0.0000370 AC: 54AN: 1461018Hom.: 0 Cov.: 33 AF XY: 0.0000468 AC XY: 34AN XY: 726852
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2019 | The p.R359C variant (also known as c.1075C>T), located in coding exon 9 of the CCDC114 gene, results from a C to T substitution at nucleotide position 1075. The arginine at codon 359 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This sequence change replaces arginine with cysteine at codon 359 of the CCDC114 protein (p.Arg359Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs373501045, ExAC 0.03%). This variant has not been reported in the literature in individuals with CCDC114-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at