rs199503571
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_181426.2(CCDC39):āc.1818T>Cā(p.His606=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,609,826 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00046 ( 0 hom., cov: 32)
Exomes š: 0.00049 ( 1 hom. )
Consequence
CCDC39
NM_181426.2 synonymous
NM_181426.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.371
Genes affected
CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 3-180642049-A-G is Benign according to our data. Variant chr3-180642049-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 344265.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.371 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.1818T>C | p.His606= | synonymous_variant | 13/20 | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.1818T>C | p.His606= | synonymous_variant | 13/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000490 AC: 121AN: 246826Hom.: 0 AF XY: 0.000493 AC XY: 66AN XY: 133838
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GnomAD4 exome AF: 0.000486 AC: 708AN: 1457566Hom.: 1 Cov.: 30 AF XY: 0.000459 AC XY: 333AN XY: 724904
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GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35AN XY: 74462
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2022 | This alteration is classified as likely 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. - |
Primary ciliary dyskinesia 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at