rs868938106

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031421.5(ODAD4):​c.316C>G​(p.Arg106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ODAD4
NM_031421.5 missense

Scores

6
7
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10
Variant links:
Genes affected
ODAD4 (HGNC:25280): (outer dynein arm docking complex subunit 4) This gene encodes a tetratricopeptide repeat domain-containing protein that localizes to ciliary axonmenes and plays a role in the docking of the outer dynein arm to cilia. Mutations in this gene cause severely reduced ciliary motility and the disorder CILD35 (ciliary dyskinesia,primary, 35). Primary ciliary dyskinesia is often associated with recurrent respiratory infections, immotile spermatozoa, and situs inversus; an inversion in left-right body symmetry. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ODAD4NM_031421.5 linkc.316C>G p.Arg106Gly missense_variant Exon 3 of 12 ENST00000377540.6 NP_113609.1 Q96NG3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ODAD4ENST00000377540.6 linkc.316C>G p.Arg106Gly missense_variant Exon 3 of 12 1 NM_031421.5 ENSP00000478589.1 Q96NG3-1
ODAD4ENST00000591658.5 linkn.316C>G non_coding_transcript_exon_variant Exon 3 of 10 5 ENSP00000477931.1 A0A087WTJ8
ODAD4ENST00000585530.1 linkn.*61+125C>G intron_variant Intron 2 of 3 3 ENSP00000479460.1 A0A087WVI5
ODAD4ENST00000593239.5 linkn.*61+125C>G intron_variant Intron 3 of 5 3 ENSP00000484975.1 A0A087X2G9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461300
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726890
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.28
T
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
-0.060
T
PrimateAI
Pathogenic
0.80
T
REVEL
Uncertain
0.49
Sift4G
Uncertain
0.0070
D
Polyphen
1.0
D
Vest4
0.89
MutPred
0.71
Gain of ubiquitination at K109 (P = 0.0594);
MVP
0.25
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.86
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40091921; API