rs61741137

Positions:

chr19-11434844-A-G

Variant summary

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

The ENST00000356392.9(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. 14/20 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
ENST00000356392.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.509

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=0.0034710765).

BP6

Variant 19-11434844-A-G is Benign according to our data. Variant chr19-11434844-A-G is described in ClinVar as [Benign]. Clinvar id is 221005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11434844-A-G is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ODAD3	NM_145045.5 linkuse as main transcript	c.173T>C	p.Phe58Ser	missense_variant	1/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302454.2 linkuse as main transcript	c.173T>C	p.Phe58Ser	missense_variant	1/11		NP_001289383.1
ODAD3	XM_017026241.2 linkuse as main transcript	c.173T>C	p.Phe58Ser	missense_variant	1/9		XP_016881730.1
ODAD3	NM_001302453.1 linkuse as main transcript	c.82+846T>C		intron_variant			NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.173T>C	p.Phe58Ser	missense_variant	1/13	1	NM_145045.5	ENSP00000348757	P2	A5D8V7-1

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

GnomAD3 exomes

AF:

0.00855

AC:

2133

AN:

249532

Hom.:

AF XY:

0.00892

AC XY:

1208

AN XY:

135384

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 SAS exome

AF:

0.00755

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

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00788

Gnomad4 FIN exome

AF:

0.00536

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00737

AC:

1122

AN:

152286

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

490

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.00757

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ODAD3: BP4, BS1, BS2 -

Primary ciliary dyskinesia 30

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

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;.

MutationTaster

Benign

1.0

N;N;N;N

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

Varity_R

0.043

gMVP

0.15

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