chr3-180663940-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_181426.2(CCDC39):c.137G>A(p.Arg46His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,611,806 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 (★★).
Frequency
Consequence
NM_181426.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.137G>A | p.Arg46His | missense_variant | 2/20 | ENST00000476379.6 | NP_852091.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.137G>A | p.Arg46His | missense_variant | 2/20 | 2 | NM_181426.2 | ENSP00000417960 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000524 AC: 13AN: 248268Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134780
GnomAD4 exome AF: 0.0000596 AC: 87AN: 1459540Hom.: 0 Cov.: 29 AF XY: 0.0000537 AC XY: 39AN XY: 726276
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74454
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 07, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 46 of the CCDC39 protein (p.Arg46His). This variant is present in population databases (rs376716008, gnomAD 0.008%). 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: 569732). 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 histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2023 | The c.137G>A (p.R46H) alteration is located in exon 2 (coding exon 2) of the CCDC39 gene. This alteration results from a G to A substitution at nucleotide position 137, causing the arginine (R) at amino acid position 46 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Primary ciliary dyskinesia 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 03, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at