19-55160687-A-G

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.1001T>C(p.Leu334Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,613,638 control chromosomes in the GnomAD database, including 6,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 716 hom., cov: 32)

Exomes 𝑓: 0.048 ( 5484 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.170

Publications

17 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:

ENSG00000267110 (HGNC:):

ENSG00000267110 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=0.004614681).

BP6

Variant 19-55160687-A-G is Benign according to our data. Variant chr19-55160687-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257679.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256715.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF3	NM_001256715.2	MANE Select	c.1001T>C	p.Leu334Pro	missense	Exon 9 of 12	NP_001243644.1
DNAAF3	NM_001256714.1		c.1205T>C	p.Leu402Pro	missense	Exon 9 of 12	NP_001243643.1
DNAAF3	NM_178837.4		c.1142T>C	p.Leu381Pro	missense	Exon 9 of 12	NP_849159.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.1001T>C	p.Leu334Pro	missense	Exon 9 of 12	ENSP00000432046.3
DNAAF3	ENST00000455045.5	TSL:1	c.839T>C	p.Leu280Pro	missense	Exon 9 of 12	ENSP00000394343.1
DNAAF3	ENST00000528412.5	TSL:1	n.*789T>C		non_coding_transcript_exon	Exon 9 of 12	ENSP00000433826.2

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9217

AN:

152094

Hom.:

706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0214

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.0883

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0680

GnomAD2 exomes

AF:

0.0979

AC:

24271

AN:

248004

AF XY:

0.0855

show subpopulations

Gnomad AFR exome

AF:

0.0506

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0478

AC:

69810

AN:

1461426

Hom.:

5484

Cov.:

AF XY:

0.0472

AC XY:

34326

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.0496

AC:

1662

AN:

33478

American (AMR)

AF:

0.357

AC:

15958

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0214

AC:

560

AN:

26124

East Asian (EAS)

AF:

0.242

AC:

9612

AN:

39686

South Asian (SAS)

AF:

0.0832

AC:

7178

AN:

86252

European-Finnish (FIN)

AF:

0.0319

AC:

1692

AN:

53082

Middle Eastern (MID)

AF:

0.0366

AC:

211

AN:

5764

European-Non Finnish (NFE)

AF:

0.0267

AC:

29661

AN:

1111944

Other (OTH)

AF:

0.0542

AC:

3276

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

3674

7348

11022

14696

18370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1478

2956

4434

5912

7390

<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:

0.0608

AC:

9249

AN:

152212

Hom.:

716

Cov.:

AF XY:

0.0645

AC XY:

4799

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0504

AC:

2095

AN:

41558

American (AMR)

AF:

0.214

AC:

3264

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0214

AC:

AN:

3466

East Asian (EAS)

AF:

0.221

AC:

1134

AN:

5130

South Asian (SAS)

AF:

0.0884

AC:

427

AN:

4832

European-Finnish (FIN)

AF:

0.0277

AC:

294

AN:

10610

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1810

AN:

68012

Other (OTH)

AF:

0.0678

AC:

143

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

402

805

1207

1610

2012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0450

Hom.:

1183

Bravo

AF:

0.0772

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0288

AC:

111

ESP6500AA

AF:

0.0394

AC:

152

ESP6500EA

AF:

0.0213

AC:

176

ExAC

AF:

0.0859

AC:

10383

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

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:Likely 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.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.8

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.00055

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

PhyloP100

-0.17

PrimateAI

Benign

0.43

PROVEAN

Benign

2.4

REVEL

Benign

0.28

Sift

Benign

0.34

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.035

MPC

0.36

ClinPred

0.0080

GERP RS

1.5

PromoterAI

0.072

Neutral

(source)

Varity_R

0.066

gMVP

0.55

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over