19-55160006-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001256715.2(DNAAF3):c.1056G>A(p.Pro352Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,302,950 control chromosomes in the GnomAD database, including 38,891 homozygotes. In-silico tool predicts 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. P352P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.30 ( 9058 hom., cov: 30)

Exomes 𝑓: 0.23 ( 29833 hom. )

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -2.22

Publications

34 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:

ENSG00000267110 (HGNC:):

ENSG00000267110 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.132).

BP6

Variant 19-55160006-C-T is Benign according to our data. Variant chr19-55160006-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 link	c.1056G>A	p.Pro352Pro	synonymous_variant	Exon 10 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.1056G>A	p.Pro352Pro	synonymous_variant	Exon 10 of 12	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1
ENSG00000267110	ENST00000587871.1 link	n.39G>A		non_coding_transcript_exon_variant	Exon 2 of 9	5		ENSP00000473050.1		M0R381

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

44409

AN:

147808

Hom.:

9032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.284

GnomAD2 exomes

AF:

0.214

AC:

53257

AN:

248376

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.234

AC:

270117

AN:

1155012

Hom.:

29833

Cov.:

AF XY:

0.235

AC XY:

136480

AN XY:

581438

show subpopulations

African (AFR)

AF:

0.628

AC:

19401

AN:

30890

American (AMR)

AF:

0.144

AC:

5889

AN:

40894

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

4569

AN:

20706

East Asian (EAS)

AF:

0.238

AC:

7025

AN:

29540

South Asian (SAS)

AF:

0.290

AC:

23754

AN:

81998

European-Finnish (FIN)

AF:

0.247

AC:

10536

AN:

42644

Middle Eastern (MID)

AF:

0.323

AC:

1498

AN:

4636

European-Non Finnish (NFE)

AF:

0.216

AC:

184591

AN:

856338

Other (OTH)

AF:

0.271

AC:

12854

AN:

47366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

9679

19358

29037

38716

48395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6592

13184

19776

26368

32960

<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:

0.301

AC:

44481

AN:

147938

Hom.:

9058

Cov.:

AF XY:

0.298

AC XY:

21467

AN XY:

72102

show subpopulations

African (AFR)

AF:

0.589

AC:

23890

AN:

40552

American (AMR)

AF:

0.192

AC:

2836

AN:

14794

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

620

AN:

3430

East Asian (EAS)

AF:

0.233

AC:

1100

AN:

4728

South Asian (SAS)

AF:

0.307

AC:

1369

AN:

4464

European-Finnish (FIN)

AF:

0.211

AC:

2053

AN:

9746

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11796

AN:

66964

Other (OTH)

AF:

0.290

AC:

602

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1202

2404

3605

4807

6009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.234

Hom.:

11895

Bravo

AF:

0.308

Asia WGS

AF:

0.313

AC:

1084

AN:

3476

EpiCase

AF:

0.184

EpiControl

AF:

0.183

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

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 -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 2

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: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 09, 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

- -

Hypertrophic cardiomyopathy

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.93

(source)

DANN

Benign

0.92

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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