17-80058885-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017950.4(CCDC40):c.1345C>G(p.Arg449Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_017950.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.1345C>G | p.Arg449Gly | missense_variant | Exon 9 of 20 | ENST00000397545.9 | NP_060420.2 | |
CCDC40 | NM_001243342.2 | c.1345C>G | p.Arg449Gly | missense_variant | Exon 9 of 18 | NP_001230271.1 | ||
CCDC40 | NM_001330508.2 | c.1345C>G | p.Arg449Gly | missense_variant | Exon 9 of 11 | NP_001317437.1 | ||
LOC124904074 | XR_007065931.1 | n.906G>C | non_coding_transcript_exon_variant | Exon 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 449 of the CCDC40 protein (p.Arg449Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant has not been reported in the literature in individuals with CCDC40-related disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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