rs1053136709
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_145045.5(ODAD3):c.1035G>C(p.Glu345Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,232 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
ODAD3
NM_145045.5 missense
NM_145045.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 0.507
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 Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26093405).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000103 (15/1461160) while in subpopulation AFR AF= 0.000448 (15/33480). AF 95% confidence interval is 0.000276. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ODAD3 | NM_145045.5 | c.1035G>C | p.Glu345Asp | missense_variant | 8/13 | ENST00000356392.9 | |
ODAD3 | NM_001302453.1 | c.873G>C | p.Glu291Asp | missense_variant | 8/13 | ||
ODAD3 | NM_001302454.2 | c.855G>C | p.Glu285Asp | missense_variant | 6/11 | ||
ODAD3 | XM_017026241.2 | c.976G>C | p.Ala326Pro | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ODAD3 | ENST00000356392.9 | c.1035G>C | p.Glu345Asp | missense_variant | 8/13 | 1 | NM_145045.5 | P2 | |
ODAD3 | ENST00000591179.5 | c.855G>C | p.Glu285Asp | missense_variant | 6/11 | 1 | A2 | ||
ODAD3 | ENST00000586836.5 | c.462G>C | p.Glu154Asp | missense_variant | 8/13 | 2 | A2 | ||
ODAD3 | ENST00000591345.5 | c.*954G>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152072Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
12
AN:
152072
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249060Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135174
GnomAD3 exomes
AF:
AC:
2
AN:
249060
Hom.:
AF XY:
AC XY:
1
AN XY:
135174
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461160Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 726908
GnomAD4 exome
AF:
AC:
15
AN:
1461160
Hom.:
Cov.:
34
AF XY:
AC XY:
6
AN XY:
726908
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152072Hom.: 0 Cov.: 30 AF XY: 0.0000539 AC XY: 4AN XY: 74272
GnomAD4 genome
?
AF:
AC:
12
AN:
152072
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
74272
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 | Sep 09, 2016 | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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 replaces glutamic acid with aspartic acid at codon 345 of the CCDC151 protein (p.Glu345Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.
REVEL
Uncertain
Sift
Benign
T;.;.
Sift4G
Benign
T;T;T
Polyphen
P;.;.
Vest4
MutPred
Loss of disorder (P = 0.1865);.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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