Genetic Variant DNAAF3:p.Asp244Asn (chr19-55161352-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001256715.2(DNAAF3):c.730G>A(p.Asp244Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,610,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D244Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.11

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.730G>A	p.Asp244Asn	missense	Exon 7 of 12	NP_001243644.1	Q8N9W5-1
DNAAF3	NM_001256714.1		c.934G>A	p.Asp312Asn	missense	Exon 7 of 12	NP_001243643.1	Q8N9W5-3
DNAAF3	NM_178837.4		c.871G>A	p.Asp291Asn	missense	Exon 7 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.730G>A	p.Asp244Asn	missense	Exon 7 of 12	ENSP00000432046.3	Q8N9W5-1
DNAAF3	ENST00000455045.5	TSL:1	c.568G>A	p.Asp190Asn	missense	Exon 7 of 12	ENSP00000394343.1	Q8N9W5-7
DNAAF3	ENST00000528412.5	TSL:1	n.*518G>A		non_coding_transcript_exon	Exon 7 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.00

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111418

Other (OTH)

AF:

0.00

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000663

AC:

AN:

150750

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40924

American (AMR)

AF:

0.00

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5036

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67724

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.54

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

PhyloP100

3.1

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.11

Sift

Uncertain

0.011

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.65

MutPred

0.39

Loss of sheet (P = 0.0357)

MVP

0.68

MPC

0.83

ClinPred

0.98

GERP RS

4.2

Varity_R

0.37

gMVP

0.52

Mutation Taster

=89/11

polymorphism

(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