rs780264719
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_181426.2(CCDC39):c.1436C>T(p.Ala479Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,610,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A479A) has been classified as Likely benign.
Frequency
Consequence
NM_181426.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.1436C>T | p.Ala479Val | missense_variant | 11/20 | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.1436C>T | p.Ala479Val | missense_variant | 11/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000463 AC: 7AN: 151174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000324 AC: 8AN: 247092Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134140
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459136Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 725752
GnomAD4 genome ? AF: 0.0000463 AC: 7AN: 151174Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3AN XY: 73756
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2021 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 479 of the CCDC39 protein (p.Ala479Val). This variant is present in population databases (rs780264719, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CCDC39-related conditions. ClinVar contains an entry for this variant (Variation ID: 577631). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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