rs149158199

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178452.6(DNAAF1):c.1303G>A(p.Asp435Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,590,246 control chromosomes in the GnomAD database, including 756 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 65 hom., cov: 32)

Exomes 𝑓: 0.029 ( 691 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.03

Publications

10 publications found

Variant links:

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 13
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAAF1 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=0.0034924448).

BP6

Variant 16-84170131-G-A is Benign according to our data. Variant chr16-84170131-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0268 (4073/152082) while in subpopulation NFE AF = 0.0335 (2276/67958). AF 95% confidence interval is 0.0323. There are 65 homozygotes in GnomAd4. There are 1867 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 65 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	NM_178452.6	MANE Select	c.1303G>A	p.Asp435Asn	missense	Exon 8 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.595G>A	p.Asp199Asn	missense	Exon 4 of 8	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.1303G>A	p.Asp435Asn	missense	Exon 8 of 12	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000963697.1		c.1303G>A	p.Asp435Asn	missense	Exon 8 of 13	ENSP00000633756.1
DNAAF1	ENST00000963694.1		c.1303G>A	p.Asp435Asn	missense	Exon 8 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4067

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0381

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0353

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0251

AC:

6298

AN:

251304

AF XY:

0.0253

show subpopulations

Gnomad AFR exome

AF:

0.0216

Gnomad AMR exome

AF:

0.0222

Gnomad ASJ exome

AF:

0.0408

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0288

AC:

41467

AN:

1438164

Hom.:

691

Cov.:

AF XY:

0.0287

AC XY:

20530

AN XY:

714870

show subpopulations

African (AFR)

AF:

0.0193

AC:

635

AN:

32928

American (AMR)

AF:

0.0229

AC:

1002

AN:

43840

Ashkenazi Jewish (ASJ)

AF:

0.0433

AC:

1090

AN:

25194

East Asian (EAS)

AF:

0.00

AC:

AN:

36818

South Asian (SAS)

AF:

0.0127

AC:

1063

AN:

83440

European-Finnish (FIN)

AF:

0.0192

AC:

1020

AN:

52998

Middle Eastern (MID)

AF:

0.0485

AC:

269

AN:

5548

European-Non Finnish (NFE)

AF:

0.0315

AC:

34600

AN:

1098414

Other (OTH)

AF:

0.0303

AC:

1788

AN:

58984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3036

6071

9107

12142

15178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1254

2508

3762

5016

6270

<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:

0.0268

AC:

4073

AN:

152082

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1867

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0221

AC:

916

AN:

41494

American (AMR)

AF:

0.0270

AC:

412

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0381

AC:

132

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.0116

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10588

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0335

AC:

2276

AN:

67958

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

192

385

577

770

962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0299

Hom.:

124

Bravo

AF:

0.0272

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0376

AC:

145

ESP6500AA

AF:

0.0264

AC:

116

ESP6500EA

AF:

0.0338

AC:

291

ExAC

AF:

0.0252

AC:

3062

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0382

EpiControl

AF:

0.0410

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 13 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.5

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.55

REVEL

Benign

0.071

Sift

Benign

0.038

Sift4G

Benign

0.42

Polyphen

0.61

Vest4

0.028

MPC

0.084

ClinPred

0.012

GERP RS

1.2

Varity_R

0.051

gMVP

0.082

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