NM_178452.6:c.919C>G

Variant names:

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.919C>G(p.Gln307Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,613,316 control chromosomes in the GnomAD database, including 599 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 Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 101 hom., cov: 31)

Exomes 𝑓: 0.023 ( 498 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.272

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=0.0020638406).

BP6

Variant 16-84165838-C-G is Benign according to our data. Variant chr16-84165838-C-G is described in ClinVar as Benign. ClinVar VariationId is 163083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0301 (4557/151586) while in subpopulation AFR AF = 0.0466 (1924/41284). AF 95% confidence interval is 0.0449. There are 101 homozygotes in GnomAd4. There are 2253 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 101 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.919C>G	p.Gln307Glu	missense	Exon 7 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.163C>G	p.Gln55Glu	missense	Exon 3 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.919C>G	p.Gln307Glu	missense	Exon 7 of 12	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000963697.1		c.919C>G	p.Gln307Glu	missense	Exon 7 of 13	ENSP00000633756.1
DNAAF1	ENST00000963694.1		c.919C>G	p.Gln307Glu	missense	Exon 7 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4546

AN:

151466

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0246

GnomAD2 exomes

AF:

0.0205

AC:

5153

AN:

251410

AF XY:

0.0196

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0610

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0227

AC:

33224

AN:

1461730

Hom.:

498

Cov.:

AF XY:

0.0222

AC XY:

16136

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.0467

AC:

1562

AN:

33468

American (AMR)

AF:

0.00859

AC:

384

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

401

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00189

AC:

163

AN:

86254

European-Finnish (FIN)

AF:

0.0615

AC:

3284

AN:

53402

Middle Eastern (MID)

AF:

0.00543

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0235

AC:

26165

AN:

1111954

Other (OTH)

AF:

0.0204

AC:

1234

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1762

3524

5286

7048

8810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

986

1972

2958

3944

4930

<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:

0.0301

AC:

4557

AN:

151586

Hom.:

101

Cov.:

AF XY:

0.0304

AC XY:

2253

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.0466

AC:

1924

AN:

41284

American (AMR)

AF:

0.00989

AC:

150

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.000832

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0677

AC:

708

AN:

10460

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0244

AC:

1661

AN:

67954

Other (OTH)

AF:

0.0243

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

200

399

599

798

998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0223

Hom.:

Bravo

AF:

0.0261

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.0391

AC:

172

ESP6500EA

AF:

0.0236

AC:

203

ExAC

AF:

0.0202

AC:

2451

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 13 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.0

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.89

PhyloP100

0.27

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.010

REVEL

Benign

0.092

Sift

Benign

0.57

Sift4G

Benign

0.88

Polyphen

0.0070

Vest4

0.029

MPC

0.021

ClinPred

0.0055

GERP RS

-2.5

Varity_R

0.055

gMVP

0.22

Mutation Taster

=93/7

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