rs143192349

Positions:

chr19-11431011-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_145045.5(ODAD3):c.254G>A(p.Arg85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,614,066 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0056 ( 34 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 3.24

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:

ODAD3 (HGNC:):

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014934778).

BP6

Variant 19-11431011-C-T is Benign according to our data. Variant chr19-11431011-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 414142.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2, Benign=1}. Variant chr19-11431011-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00344 (523/152196) while in subpopulation SAS AF= 0.0079 (38/4812). AF 95% confidence interval is 0.00591. There are 1 homozygotes in gnomad4. There are 240 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/13	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	2/13		NP_001289382.1	A5D8V7-2
ODAD3	NM_001302454.2 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/11		NP_001289383.1	K7EN59
ODAD3	XM_017026241.2 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/9		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	2/13	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

523

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00789

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00584

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00369

AC:

920

AN:

249482

Hom.:

AF XY:

0.00396

AC XY:

536

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.000905

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.000929

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00445

GnomAD4 exome

AF:

0.00556

AC:

8133

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

4134

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00773

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00633

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.00344

AC:

523

AN:

152196

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

240

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00790

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00584

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00324

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000524

AC:

ESP6500EA

AF:

0.00497

AC:

ExAC

AF:

0.00413

AC:

499

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00385

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 16, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Johns Hopkins Genomics, Johns Hopkins University	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	Feb 18, 2020	- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.254G>A (p.R85Q) alteration is located in exon 2 (coding exon 2) of the CCDC151 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the arginine (R) at amino acid position 85 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2023

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.19

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.22

T;T

Polyphen

0.99

D;.

Vest4

0.71

MVP

0.84

MPC

1.4

ClinPred

0.036

GERP RS

3.8

Varity_R

0.21

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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