rs61739927

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145045.5(ODAD3):c.424C>G(p.Leu142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,614,046 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 64 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.07

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010106593).

BP6

Variant 19-11430719-G-C is Benign according to our data. Variant chr19-11430719-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 414138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11430719-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1816/152174) while in subpopulation AFR AF= 0.0233 (966/41522). AF 95% confidence interval is 0.022. There are 26 homozygotes in gnomad4. There are 921 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5 link	c.424C>G	p.Leu142Val	missense_variant	Exon 3 of 13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 link	c.262C>G	p.Leu88Val	missense_variant	Exon 3 of 13		NP_001289382.1	A5D8V7-2
ODAD3	XM_017026241.2 link	c.424C>G	p.Leu142Val	missense_variant	Exon 3 of 9		XP_016881730.1
ODAD3	NM_001302454.2 link	c.366+180C>G		intron_variant	Intron 2 of 10		NP_001289383.1	K7EN59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.424C>G	p.Leu142Val	missense_variant	Exon 3 of 13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1787

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.00525

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00792

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.00735

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00794

AC:

1981

AN:

249508

Hom.:

AF XY:

0.00825

AC XY:

1116

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00795

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.00672

Gnomad NFE exome

AF:

0.00719

Gnomad OTH exome

AF:

0.00727

GnomAD4 exome

AF:

0.00814

AC:

11900

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6038

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00411

Gnomad4 SAS exome

AF:

0.0129

Gnomad4 FIN exome

AF:

0.00545

Gnomad4 NFE exome

AF:

0.00795

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.0119

AC:

1816

AN:

152174

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

921

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.00524

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00794

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.00735

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.00948

Alfa

AF:

0.00812

Hom.:

Bravo

AF:

0.0124

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0219

AC:

ESP6500EA

AF:

0.00704

AC:

ExAC

AF:

0.00839

AC:

1015

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00741

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Benign:2

Nov 09, 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 provided

Benign:2

Apr 21, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.34

Sift

Benign

0.11

Sift4G

Benign

0.29

Polyphen

0.95

Vest4

0.49

MVP

0.81

MPC

1.2

ClinPred

0.013

GERP RS

0.47

Varity_R

0.069

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over