NM_001256715.2:c.529G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256715.2(DNAAF3):c.529G>A(p.Gly177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,500,488 control chromosomes in the GnomAD database, including 4,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G177G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.062 ( 741 hom., cov: 32)

Exomes 𝑓: 0.046 ( 4135 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.0640

Publications

13 publications found

Variant links:

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

DNAAF3 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048737824).

BP6

Variant 19-55161777-C-T is Benign according to our data. Variant chr19-55161777-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 link	c.529G>A	p.Gly177Ser	missense_variant	Exon 6 of 12	ENST00000524407.7	NP_001243644.1	Q8N9W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 link	c.529G>A	p.Gly177Ser	missense_variant	Exon 6 of 12	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9397

AN:

152182

Hom.:

730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0721

GnomAD2 exomes

AF:

0.120

AC:

12739

AN:

106158

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.0457

AC:

61651

AN:

1348188

Hom.:

4135

Cov.:

AF XY:

0.0469

AC XY:

30994

AN XY:

661510

show subpopulations

African (AFR)

AF:

0.0490

AC:

1462

AN:

29844

American (AMR)

AF:

0.333

AC:

9840

AN:

29530

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

496

AN:

22662

East Asian (EAS)

AF:

0.241

AC:

8400

AN:

34870

South Asian (SAS)

AF:

0.114

AC:

8415

AN:

74004

European-Finnish (FIN)

AF:

0.0333

AC:

1295

AN:

38920

Middle Eastern (MID)

AF:

0.0399

AC:

165

AN:

4134

European-Non Finnish (NFE)

AF:

0.0269

AC:

28435

AN:

1058398

Other (OTH)

AF:

0.0563

AC:

3143

AN:

55826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3079

6158

9238

12317

15396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1356

2712

4068

5424

6780

<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:

0.0619

AC:

9430

AN:

152300

Hom.:

741

Cov.:

AF XY:

0.0664

AC XY:

4944

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0493

AC:

2050

AN:

41566

American (AMR)

AF:

0.214

AC:

3270

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1137

AN:

5164

South Asian (SAS)

AF:

0.129

AC:

624

AN:

4832

European-Finnish (FIN)

AF:

0.0276

AC:

293

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0268

AC:

1820

AN:

68030

Other (OTH)

AF:

0.0728

AC:

154

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

414

827

1241

1654

2068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0424

Hom.:

902

Bravo

AF:

0.0770

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.0370

AC:

136

ESP6500EA

AF:

0.0234

AC:

184

ExAC

AF:

0.0479

AC:

4867

Asia WGS

AF:

0.193

AC:

672

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 22, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated Cardiomyopathy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial restrictive cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.5

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.00061

.;T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

.;M;.;.

PhyloP100

0.064

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.63

N;.;.;N

REVEL

Benign

0.046

Sift

Benign

0.61

T;.;.;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.62

.;P;.;.

Vest4

0.083

MPC

1.5

ClinPred

0.0065

GERP RS

2.5

Varity_R

0.035

gMVP

0.52

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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