NM_145045.5:c.145A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145045.5(ODAD3):c.145A>C(p.Thr49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,098 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 150 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 188 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.131

Publications

1 publications found

Variant links:

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]

ODAD3 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 30
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00212273).

BP6

Variant 19-11434872-T-G is Benign according to our data. Variant chr19-11434872-T-G is described in ClinVar as Benign. ClinVar VariationId is 414144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5 link	c.145A>C	p.Thr49Pro	missense_variant	Exon 1 of 13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302454.2 link	c.145A>C	p.Thr49Pro	missense_variant	Exon 1 of 11		NP_001289383.1	K7EN59
ODAD3	XM_017026241.2 link	c.145A>C	p.Thr49Pro	missense_variant	Exon 1 of 9		XP_016881730.1
ODAD3	NM_001302453.1 link	c.82+818A>C		intron_variant	Intron 1 of 12		NP_001289382.1	A5D8V7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.145A>C	p.Thr49Pro	missense_variant	Exon 1 of 13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3824

AN:

152122

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.00646

AC:

1611

AN:

249490

AF XY:

0.00493

show subpopulations

Gnomad AFR exome

AF:

0.0885

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000389

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00278

AC:

4070

AN:

1461856

Hom.:

188

Cov.:

AF XY:

0.00243

AC XY:

1770

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0933

AC:

3125

AN:

33480

American (AMR)

AF:

0.00519

AC:

232

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000202

AC:

225

AN:

1112010

Other (OTH)

AF:

0.00647

AC:

391

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

230

459

689

918

1148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0252

AC:

3844

AN:

152242

Hom.:

150

Cov.:

AF XY:

0.0240

AC XY:

1789

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0871

AC:

3617

AN:

41524

American (AMR)

AF:

0.00988

AC:

151

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68020

Other (OTH)

AF:

0.0204

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

181

362

542

723

904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0296

ESP6500AA

AF:

0.0745

AC:

294

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00757

AC:

915

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 30

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.29

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.00066

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.096

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-1.1

N;.

PhyloP100

-0.13

PrimateAI

Benign

0.25

PROVEAN

Benign

0.47

N;.

REVEL

Benign

0.016

Sift

Benign

0.92

T;.

Sift4G

Benign

0.65

T;T

Polyphen

0.0

B;.

Vest4

0.14

MVP

0.072

MPC

0.58

ClinPred

0.0060

GERP RS

-0.50

PromoterAI

0.061

Neutral

(source)

Varity_R

0.066

gMVP

0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over