rs143287033

chr19-11426959-T-Achr19-11426959-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145045.5(ODAD3):c.526A>T(p.Arg176Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,608,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R176G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4030915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.526A>T	p.Arg176Trp	missense_variant	4/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.364A>T	p.Arg122Trp	missense_variant	4/13
ODAD3	NM_001302454.2	c.448A>T	p.Arg150Trp	missense_variant	3/11
ODAD3	XM_017026241.2	c.526A>T	p.Arg176Trp	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.526A>T	p.Arg176Trp	missense_variant	4/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.448A>T	p.Arg150Trp	missense_variant	3/11	1		A2
ODAD3	ENST00000586836.5	c.-48A>T		5_prime_UTR_variant	4/13	2		A2
ODAD3	ENST00000591345.5	c.*445A>T		3_prime_UTR_variant, NMD_transcript_variant	5/14	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456570 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724880

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74344

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	0.070
Eigen_PC	Benign	-0.0065
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.3	D;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0020	D;T
Polyphen		0.98	D;.
Vest4		0.35
MutPred		0.40		Loss of disorder (P = 0.0252);.;
MVP		0.80
MPC		1.3
ClinPred		0.96	D
GERP RS		1.1
Varity_R		0.12
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs143287033; hg19: chr19-11537779;