chr19-55161102-T-C

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.875A>G(p.Glu292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,543,812 control chromosomes in the GnomAD database, including 25,671 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E292V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.24 ( 6211 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19460 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.950

Publications

24 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=3.026724E-4).

BP6

Variant 19-55161102-T-C is Benign according to our data. Variant chr19-55161102-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 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	UniProt
DNAAF3	NM_001256715.2	MANE Select	c.875A>G	p.Glu292Gly	missense	Exon 8 of 12	NP_001243644.1	Q8N9W5-1
DNAAF3	NM_001256714.1		c.1079A>G	p.Glu360Gly	missense	Exon 8 of 12	NP_001243643.1	Q8N9W5-3
DNAAF3	NM_178837.4		c.1016A>G	p.Glu339Gly	missense	Exon 8 of 12	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.875A>G	p.Glu292Gly	missense	Exon 8 of 12	ENSP00000432046.3	Q8N9W5-1
DNAAF3	ENST00000455045.5	TSL:1	c.713A>G	p.Glu238Gly	missense	Exon 8 of 12	ENSP00000394343.1	Q8N9W5-7
DNAAF3	ENST00000528412.5	TSL:1	n.*663A>G		non_coding_transcript_exon	Exon 8 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36390

AN:

151792

Hom.:

6195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.0832

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0990

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.240

GnomAD2 exomes

AF:

0.159

AC:

23233

AN:

146054

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.0796

Gnomad FIN exome

AF:

0.0948

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.155

AC:

215579

AN:

1391902

Hom.:

19460

Cov.:

AF XY:

0.154

AC XY:

105741

AN XY:

686722

show subpopulations

African (AFR)

AF:

0.498

AC:

15682

AN:

31498

American (AMR)

AF:

0.126

AC:

4490

AN:

35672

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

6395

AN:

25142

East Asian (EAS)

AF:

0.0513

AC:

1832

AN:

35708

South Asian (SAS)

AF:

0.137

AC:

10870

AN:

79164

European-Finnish (FIN)

AF:

0.105

AC:

4598

AN:

43906

Middle Eastern (MID)

AF:

0.281

AC:

1272

AN:

4522

European-Non Finnish (NFE)

AF:

0.148

AC:

159902

AN:

1078496

Other (OTH)

AF:

0.182

AC:

10538

AN:

57794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

11507

23015

34522

46030

57537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5920

11840

17760

23680

29600

<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:

0.240

AC:

36452

AN:

151910

Hom.:

6211

Cov.:

AF XY:

0.231

AC XY:

17183

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.484

AC:

20035

AN:

41402

American (AMR)

AF:

0.165

AC:

2523

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

894

AN:

3464

East Asian (EAS)

AF:

0.0828

AC:

423

AN:

5108

South Asian (SAS)

AF:

0.136

AC:

653

AN:

4810

European-Finnish (FIN)

AF:

0.0990

AC:

1047

AN:

10578

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10149

AN:

67938

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1261

2523

3784

5046

6307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.182

Hom.:

12463

Bravo

AF:

0.259

TwinsUK

AF:

0.156

AC:

580

ALSPAC

AF:

0.140

AC:

541

ESP6500AA

AF:

0.367

AC:

1334

ESP6500EA

AF:

0.123

AC:

922

ExAC

AF:

0.0889

AC:

6989

Asia WGS

AF:

0.164

AC:

569

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

not provided (2)

not specified (2)

Primary ciliary dyskinesia 2 (2)

Dilated Cardiomyopathy, Recessive (1)

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome (1)

Familial restrictive cardiomyopathy (1)

Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.53

MetaRNN

Benign

0.00030

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

PhyloP100

0.95

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.088

Sift

Uncertain

0.013

Sift4G

Uncertain

0.031

Polyphen

0.76

Vest4

0.072

MPC

0.52

ClinPred

0.027

GERP RS

3.2

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.10

gMVP

0.56

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over