rs587777779
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_145045.5(ODAD3):c.925G>T(p.Glu309Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
ODAD3
NM_145045.5 stop_gained
NM_145045.5 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 2.05
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD3 | NM_145045.5 | c.925G>T | p.Glu309Ter | stop_gained | 7/13 | ENST00000356392.9 | |
ODAD3 | NM_001302453.1 | c.763G>T | p.Glu255Ter | stop_gained | 7/13 | ||
ODAD3 | NM_001302454.2 | c.745G>T | p.Glu249Ter | stop_gained | 5/11 | ||
ODAD3 | XM_017026241.2 | c.904+21G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD3 | ENST00000356392.9 | c.925G>T | p.Glu309Ter | stop_gained | 7/13 | 1 | NM_145045.5 | P2 | |
ODAD3 | ENST00000591179.5 | c.745G>T | p.Glu249Ter | stop_gained | 5/11 | 1 | A2 | ||
ODAD3 | ENST00000586836.5 | c.352G>T | p.Glu118Ter | stop_gained | 7/13 | 2 | A2 | ||
ODAD3 | ENST00000591345.5 | c.*844G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 30 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2014 | - - |
Kartagener syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at