rs1553804100
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_181426.2(CCDC39):c.1363-11A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 146,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)
Consequence
CCDC39
NM_181426.2 splice_polypyrimidine_tract, intron
NM_181426.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9977
2
Clinical Significance
Conservation
PhyloP100: 1.88
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
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Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 3-180647254-T-C is Pathogenic according to our data. Variant chr3-180647254-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 525356.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.1363-11A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.1363-11A>G | splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000682 AC: 1AN: 146686Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 29
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GnomAD4 genome ? AF: 0.00000682 AC: 1AN: 146686Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1AN XY: 71398
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 02, 2017 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual with clinical features of primary ciliary dyskinesia (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 10 of the CCDC39 gene. It does not directly change the encoded amino acid sequence of the CCDC39 protein. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -1
DS_AL_spliceai
Position offset: -11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at