NM_145045.5:c.173T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145045.5(ODAD3):c.173T>C(p.Phe58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,158 control chromosomes in the GnomAD database, including 162 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 0.0074 ( 5 hom., cov: 33)

Exomes 𝑓: 0.013 ( 157 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.509

Publications

11 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=0.0034710765).

BP6

Variant 19-11434844-A-G is Benign according to our data. Variant chr19-11434844-A-G is described in ClinVar as Benign. ClinVar VariationId is 221005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00737 (1122/152286) while in subpopulation NFE AF = 0.0125 (848/68012). AF 95% confidence interval is 0.0118. There are 5 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ODAD3	NM_145045.5 link	c.173T>C	p.Phe58Ser	missense_variant	Exon 1 of 13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302454.2 link	c.173T>C	p.Phe58Ser	missense_variant	Exon 1 of 11		NP_001289383.1
ODAD3	XM_017026241.2 link	c.173T>C	p.Phe58Ser	missense_variant	Exon 1 of 9		XP_016881730.1
ODAD3	NM_001302453.1 link	c.82+846T>C		intron_variant	Intron 1 of 12		NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.173T>C	p.Phe58Ser	missense_variant	Exon 1 of 13	1	NM_145045.5	ENSP00000348757.3

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1123

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00464

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00855

AC:

2133

AN:

249532

AF XY:

0.00892

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00422

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00908

GnomAD4 exome

AF:

0.0127

AC:

18553

AN:

1461872

Hom.:

157

Cov.:

AF XY:

0.0126

AC XY:

9151

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

33480

American (AMR)

AF:

0.00463

AC:

207

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00371

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00788

AC:

680

AN:

86254

European-Finnish (FIN)

AF:

0.00536

AC:

286

AN:

53404

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0149

AC:

16585

AN:

1112010

Other (OTH)

AF:

0.0103

AC:

625

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1156

2312

3467

4623

5779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.00737

AC:

1122

AN:

152286

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

490

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00245

AC:

102

AN:

41558

American (AMR)

AF:

0.00464

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00476

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0125

AC:

848

AN:

68012

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.0115

Hom.:

Bravo

AF:

0.00776

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0122

AC:

101

ExAC

AF:

0.00902

AC:

1090

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 16, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ODAD3: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 30

Benign:2

Oct 13, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.1

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0022

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;.

PhyloP100

-0.51

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.26

N;.

REVEL

Benign

0.0020

Sift

Benign

0.10

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.0020

B;.

Vest4

0.097

MVP

0.12

MPC

0.89

ClinPred

0.00039

GERP RS

-1.6

PromoterAI

0.017

Neutral

(source)

Varity_R

0.043

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(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