rs775366536
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_181426.2(CCDC39):c.63C>A(p.Asn21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. N21N) has been classified as Likely benign.
Frequency
Consequence
NM_181426.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.63C>A | p.Asn21Lys | missense_variant | 1/20 | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.63C>A | p.Asn21Lys | missense_variant | 1/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249222Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135202
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461646Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727104
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74248
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2023 | The c.63C>A (p.N21K) alteration is located in exon 1 (coding exon 1) of the CCDC39 gene. This alteration results from a C to A substitution at nucleotide position 63, causing the asparagine (N) at amino acid position 21 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 31, 2022 | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 21 of the CCDC39 protein (p.Asn21Lys). This variant is present in population databases (rs775366536, gnomAD 0.04%). 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: 525274). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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