chr3-180661985-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_181426.2(CCDC39):c.233G>A(p.Arg78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00647 in 1,552,978 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78C) has been classified as Uncertain significance.
Frequency
Consequence
NM_181426.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.233G>A | p.Arg78His | missense_variant | 3/20 | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.233G>A | p.Arg78His | missense_variant | 3/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00469 AC: 713AN: 152078Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00722 AC: 1159AN: 160442Hom.: 10 AF XY: 0.00804 AC XY: 679AN XY: 84444
GnomAD4 exome AF: 0.00666 AC: 9329AN: 1400782Hom.: 55 Cov.: 31 AF XY: 0.00690 AC XY: 4769AN XY: 691044
GnomAD4 genome ? AF: 0.00468 AC: 713AN: 152196Hom.: 5 Cov.: 32 AF XY: 0.00481 AC XY: 358AN XY: 74390
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | CCDC39: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 06, 2020 | This variant is associated with the following publications: (PMID: 31213628) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at