19-11420918-C-A

Position:

chr19-11420918-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_145045.5(ODAD3):c.1705G>T(p.Val569Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,962 control chromosomes in the GnomAD database, including 2 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 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.774

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059913397).

BP6

Variant 19-11420918-C-A is Benign according to our data. Variant chr19-11420918-C-A is described in ClinVar as [Benign]. Clinvar id is 241943.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000112 (17/152144) while in subpopulation SAS AF= 0.00353 (17/4816). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5 linkuse as main transcript	c.1705G>T	p.Val569Leu	missense_variant	13/13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 linkuse as main transcript	c.1543G>T	p.Val515Leu	missense_variant	13/13		NP_001289382.1	A5D8V7-2
ODAD3	NM_001302454.2 linkuse as main transcript	c.1525G>T	p.Val509Leu	missense_variant	11/11		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.1705G>T	p.Val569Leu	missense_variant	13/13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000411

AC:

102

AN:

248376

Hom.:

AF XY:

0.000504

AC XY:

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000198

AC:

290

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000112

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000488

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 31, 2022

- -

ODAD3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 23, 2023

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

0.27

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.019

T;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.032

Sift

Uncertain

0.029

D;.;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0080

B;.;.

Vest4

0.080

MutPred

0.25

Loss of MoRF binding (P = 0.1173);.;.;

MVP

0.28

MPC

0.49

ClinPred

0.021

GERP RS

1.6

Varity_R

0.24

gMVP

0.13

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