rs200773510

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS1

The NM_145045.5(ODAD3):c.1115A>T(p.His372Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000498 in 1,607,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H372Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ODAD3
NM_145045.5 missense, splice_region

Scores

Splicing: ADA: 0.9994

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.53

Publications

3 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: Likely_benign. The variant received -5 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 19-11423878-T-A is Benign according to our data. Variant chr19-11423878-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 544217.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000858 (13/151574) while in subpopulation EAS AF = 0.00235 (12/5116). AF 95% confidence interval is 0.00135. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5 link	c.1115A>T	p.His372Leu	missense_variant, splice_region_variant	Exon 8 of 13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.1115A>T	p.His372Leu	missense_variant, splice_region_variant	Exon 8 of 13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000858

AC:

AN:

151454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00234

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000232

AC:

AN:

245994

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00313

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000460

AC:

AN:

1456208

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

723964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33412

American (AMR)

AF:

0.00

AC:

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00159

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109464

Other (OTH)

AF:

0.0000665

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000858

AC:

AN:

151574

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41264

American (AMR)

AF:

0.0000657

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00235

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67894

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ODAD3-related disorder

Benign:1

Mar 16, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.072

T;T;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.028

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.67

T;T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

M;.;.

PhyloP100

1.5

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.5

D;.;.

REVEL

Uncertain

0.41

Sift

Benign

0.056

T;.;.

Sift4G

Benign

0.17

T;T;T

Polyphen

0.89

P;.;.

Vest4

0.68

MVP

0.86

MPC

1.1

ClinPred

0.19

GERP RS

3.4

Varity_R

0.28

gMVP

0.66

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.050

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