rs750861527
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001364171.2(ODAD1):c.1906G>A(p.Val636Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,788 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 (★★).
Frequency
Consequence
NM_001364171.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD1 | NM_001364171.2 | c.1906G>A | p.Val636Met | missense_variant | 16/16 | ENST00000674294.1 | |
ODAD1 | NM_144577.4 | c.1795G>A | p.Val599Met | missense_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD1 | ENST00000674294.1 | c.1906G>A | p.Val636Met | missense_variant | 16/16 | NM_001364171.2 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250956Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135698
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461788Hom.: 0 Cov.: 63 AF XY: 0.0000193 AC XY: 14AN XY: 727218
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.1795G>A (p.V599M) alteration is located in exon 14 (coding exon 13) of the CCDC114 gene. This alteration results from a G to A substitution at nucleotide position 1795, causing the valine (V) at amino acid position 599 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2019 | This sequence change replaces valine with methionine at codon 599 of the CCDC114 protein (p.Val599Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs750861527, ExAC 0.01%). This variant has not been reported in the literature in individuals with CCDC114-related disease. ClinVar contains an entry for this variant (Variation ID: 525370). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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