19-11426683-C-CATT
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_145045.5(ODAD3):c.713_714insAAT(p.Leu237_Met238insIle) variant causes a inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Consequence
ODAD3
NM_145045.5 inframe_insertion, splice_region
NM_145045.5 inframe_insertion, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.77
Genes affected
ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_145045.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD3 | NM_145045.5 | c.713_714insAAT | p.Leu237_Met238insIle | inframe_insertion, splice_region_variant | 5/13 | ENST00000356392.9 | |
ODAD3 | NM_001302453.1 | c.551_552insAAT | p.Leu183_Met184insIle | inframe_insertion, splice_region_variant | 5/13 | ||
ODAD3 | XM_017026241.2 | c.713_714insAAT | p.Leu237_Met238insIle | inframe_insertion, splice_region_variant | 5/9 | ||
ODAD3 | NM_001302454.2 | c.535-113_535-112insAAT | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD3 | ENST00000356392.9 | c.713_714insAAT | p.Leu237_Met238insIle | inframe_insertion, splice_region_variant | 5/13 | 1 | NM_145045.5 | P2 | |
ODAD3 | ENST00000591179.5 | c.535-113_535-112insAAT | intron_variant | 1 | A2 | ||||
ODAD3 | ENST00000586836.5 | c.140_141insAAT | p.Leu46_Met47insIle | inframe_insertion, splice_region_variant | 5/13 | 2 | A2 | ||
ODAD3 | ENST00000591345.5 | c.*632_*633insAAT | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 6/14 | 5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2017 | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CCDC151-related disease. This sequence change inserts 3 nucleotides in exon 5 of the CCDC151 mRNA (c.711_713dupAAT). This leads to the insertion of 1 amino acid residue in the CCDC151 protein (p.Leu237_Met238insIle) but otherwise preserves the integrity of the reading frame. In summary, this is a novel in-frame insertion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the inserted amino acid is currently unknown. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at