rs35061520

Positions:

chr19-11426783-G-A

Variant summary

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

The NM_145045.5(ODAD3):c.614C>T(p.Thr205Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 1,613,892 control chromosomes in the GnomAD database, including 686 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 39 hom., cov: 31)

Exomes 𝑓: 0.027 ( 647 hom. )

Consequence

ODAD3
NM_145045.5 missense, splice_region

Scores

Splicing: ADA: 0.0006029

Clinical Significance

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

Conservation

PhyloP100: 0.533

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=0.0039109588).

BP6

Variant 19-11426783-G-A is Benign according to our data. Variant chr19-11426783-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11426783-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2972/152238) while in subpopulation NFE AF= 0.0318 (2166/68012). AF 95% confidence interval is 0.0307. There are 39 homozygotes in gnomad4. There are 1378 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5 linkuse as main transcript	c.614C>T	p.Thr205Ile	missense_variant, splice_region_variant	5/13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant, splice_region_variant	5/13		NP_001289382.1	A5D8V7-2
ODAD3	XM_017026241.2 linkuse as main transcript	c.614C>T	p.Thr205Ile	missense_variant, splice_region_variant	5/9		XP_016881730.1
ODAD3	NM_001302454.2 linkuse as main transcript	c.534+90C>T		intron_variant			NP_001289383.1	K7EN59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.614C>T	p.Thr205Ile	missense_variant, splice_region_variant	5/13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2971

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0318

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0209

AC:

5192

AN:

248750

Hom.:

AF XY:

0.0204

AC XY:

2751

AN XY:

135012

show subpopulations

Gnomad AFR exome

AF:

0.00453

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0273

AC:

39879

AN:

1461654

Hom.:

647

Cov.:

AF XY:

0.0266

AC XY:

19334

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000997

Gnomad4 FIN exome

AF:

0.0229

Gnomad4 NFE exome

AF:

0.0325

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0195

AC:

2972

AN:

152238

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1378

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00551

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0318

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0271

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00542

AC:

ESP6500EA

AF:

0.0301

AC:

252

ExAC

AF:

0.0223

AC:

2699

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0300

EpiControl

AF:

0.0329

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2024	See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0087

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.28

Sift

Benign

0.16

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.093

B;.

Vest4

0.24

MPC

0.60

ClinPred

0.0051

GERP RS

2.5

Varity_R

0.083

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00060

dbscSNV1_RF

Benign

0.0060

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