rs56726774

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001256715.2(DNAAF3):c.510A>G(p.Val170Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,480,518 control chromosomes in the GnomAD database, including 4,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 774 hom., cov: 32)

Exomes 𝑓: 0.046 ( 4014 hom. )

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0250

Publications

9 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 19-55161796-T-C is Benign according to our data. Variant chr19-55161796-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.025 with no splicing effect.

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.510A>G	p.Val170Val	synonymous_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.510A>G	p.Val170Val	synonymous_variant	Exon 6 of 12	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1

Frequencies

GnomAD3 genomes

AF:

0.0654

AC:

9959

AN:

152184

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0612

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0750

GnomAD2 exomes

AF:

0.126

AC:

11474

AN:

90960

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.0641

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.0373

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0851

GnomAD4 exome

AF:

0.0459

AC:

60955

AN:

1328216

Hom.:

4014

Cov.:

AF XY:

0.0470

AC XY:

30499

AN XY:

649138

show subpopulations

African (AFR)

AF:

0.0625

AC:

1825

AN:

29206

American (AMR)

AF:

0.332

AC:

9346

AN:

28180

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

461

AN:

21336

East Asian (EAS)

AF:

0.241

AC:

8277

AN:

34334

South Asian (SAS)

AF:

0.114

AC:

8052

AN:

70646

European-Finnish (FIN)

AF:

0.0332

AC:

1212

AN:

36552

Middle Eastern (MID)

AF:

0.0406

AC:

174

AN:

4286

European-Non Finnish (NFE)

AF:

0.0271

AC:

28463

AN:

1048664

Other (OTH)

AF:

0.0572

AC:

3145

AN:

55012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3113

6225

9338

12450

15563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1366

2732

4098

5464

6830

<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:

0.0656

AC:

9992

AN:

152302

Hom.:

774

Cov.:

AF XY:

0.0701

AC XY:

5218

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0612

AC:

2545

AN:

41578

American (AMR)

AF:

0.216

AC:

3301

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1139

AN:

5162

South Asian (SAS)

AF:

0.129

AC:

625

AN:

4834

European-Finnish (FIN)

AF:

0.0276

AC:

293

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0271

AC:

1846

AN:

68016

Other (OTH)

AF:

0.0756

AC:

160

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

448

896

1345

1793

2241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0412

Hom.:

Bravo

AF:

0.0809

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

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

- -

Mar 22, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 08, 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

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.61

CADD

Benign

8.6

(source)

DANN

Benign

0.45

PhyloP100

-0.025

Mutation Taster

=100/0

polymorphism (auto)

(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