NM_145045.5:c.526A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_145045.5(ODAD3):c.526A>G(p.Arg176Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,608,878 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.0800

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 30
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03640431).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000328 (50/152310) while in subpopulation AMR AF = 0.00072 (11/15286). AF 95% confidence interval is 0.000403. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ODAD3	NM_145045.5 link	c.526A>G	p.Arg176Gly	missense_variant	Exon 4 of 13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1 link	c.364A>G	p.Arg122Gly	missense_variant	Exon 4 of 13		NP_001289382.1
ODAD3	NM_001302454.2 link	c.448A>G	p.Arg150Gly	missense_variant	Exon 3 of 11		NP_001289383.1
ODAD3	XM_017026241.2 link	c.526A>G	p.Arg176Gly	missense_variant	Exon 4 of 9		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.526A>G	p.Arg176Gly	missense_variant	Exon 4 of 13	1	NM_145045.5	ENSP00000348757.3

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000334

AC:

AN:

242558

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.000640

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000388

Gnomad OTH exome

AF:

0.000506

GnomAD4 exome

AF:

0.000350

AC:

510

AN:

1456568

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

254

AN XY:

724880

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33470

American (AMR)

AF:

0.000716

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48730

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000356

AC:

396

AN:

1111614

Other (OTH)

AF:

0.000464

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000328

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41586

American (AMR)

AF:

0.000720

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.000215

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Uncertain:2

Sep 06, 2019

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 176 of the CCDC151 protein (p.Arg176Gly). This variant is present in population databases (rs143287033, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CCDC151-related conditions. ClinVar contains an entry for this variant (Variation ID: 477984). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Inborn genetic diseases

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.526A>G (p.R176G) alteration is located in exon 4 (coding exon 4) of the CCDC151 gene. This alteration results from a A to G substitution at nucleotide position 526, causing the arginine (R) at amino acid position 176 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.52

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

L;.

PhyloP100

0.080

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.18

Sift

Uncertain

0.024

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

0.19

B;.

Vest4

0.28

MVP

0.77

MPC

0.77

ClinPred

0.058

GERP RS

1.1

Varity_R

0.19

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over