chr16-84176258-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178452.6(DNAAF1):c.2024G>C(p.Ser675Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,613,384 control chromosomes in the GnomAD database, including 100,057 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S675N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.29 ( 7330 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92727 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0170

Publications

34 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=9.598732E-4).

BP6

Variant 16-84176258-G-C is Benign according to our data. Variant chr16-84176258-G-C is described in ClinVar as Benign. ClinVar VariationId is 163090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

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.2024G>C	p.Ser675Thr	missense	Exon 11 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.1316G>C	p.Ser439Thr	missense	Exon 7 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.2024G>C	p.Ser675Thr	missense	Exon 11 of 12	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000963697.1		c.2030G>C	p.Ser677Thr	missense	Exon 11 of 13	ENSP00000633756.1
DNAAF1	ENST00000963694.1		c.2024G>C	p.Ser675Thr	missense	Exon 11 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43738

AN:

152012

Hom.:

7316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.294

GnomAD2 exomes

AF:

0.345

AC:

86651

AN:

250956

AF XY:

0.343

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.352

AC:

514354

AN:

1461254

Hom.:

92727

Cov.:

AF XY:

0.349

AC XY:

253641

AN XY:

726920

show subpopulations

African (AFR)

AF:

0.0965

AC:

3231

AN:

33480

American (AMR)

AF:

0.464

AC:

20730

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7767

AN:

26136

East Asian (EAS)

AF:

0.379

AC:

15041

AN:

39700

South Asian (SAS)

AF:

0.269

AC:

23188

AN:

86254

European-Finnish (FIN)

AF:

0.362

AC:

19148

AN:

52858

Middle Eastern (MID)

AF:

0.273

AC:

1575

AN:

5768

European-Non Finnish (NFE)

AF:

0.363

AC:

403812

AN:

1111952

Other (OTH)

AF:

0.329

AC:

19862

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

21352

42704

64055

85407

106759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12858

25716

38574

51432

64290

<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:

0.288

AC:

43759

AN:

152130

Hom.:

7330

Cov.:

AF XY:

0.292

AC XY:

21688

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.108

AC:

4494

AN:

41556

American (AMR)

AF:

0.390

AC:

5962

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1050

AN:

3468

East Asian (EAS)

AF:

0.374

AC:

1927

AN:

5156

South Asian (SAS)

AF:

0.271

AC:

1307

AN:

4822

European-Finnish (FIN)

AF:

0.367

AC:

3873

AN:

10558

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24051

AN:

67968

Other (OTH)

AF:

0.291

AC:

613

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1543

3087

4630

6174

7717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.324

Hom.:

6289

Bravo

AF:

0.287

TwinsUK

AF:

0.375

AC:

1391

ALSPAC

AF:

0.358

AC:

1380

ESP6500AA

AF:

0.112

AC:

491

ESP6500EA

AF:

0.356

AC:

3062

ExAC

AF:

0.337

AC:

40850

Asia WGS

AF:

0.281

AC:

975

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.347

ClinVar

ClinVar submissions

Significance: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 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.1

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.35

MetaRNN

Benign

0.00096

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

PhyloP100

-0.017

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.68

REVEL

Benign

0.049

Sift

Benign

0.45

Sift4G

Benign

0.15

Polyphen

0.021

Vest4

0.032

MPC

0.020

ClinPred

0.0032

GERP RS

-1.7

PromoterAI

0.0033

Neutral

(source)

Varity_R

0.093

gMVP

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over