Genetic Variant DNAAF3:c.323-5C>A (chr19-55162295-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001256715.2(DNAAF3):c.323-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,248,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DNAAF3
NM_001256715.2 splice_region, intron

Scores

Splicing: ADA: 0.9988

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.491

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 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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	Effect	Exon Rank	Protein
DNAAF3	NM_001256715.2	MANE Select	c.323-5C>A	splice_region intron	N/A	NP_001243644.1
DNAAF3	NM_001256714.1		c.527-5C>A	splice_region intron	N/A	NP_001243643.1
DNAAF3	NM_178837.4		c.464-5C>A	splice_region intron	N/A	NP_849159.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.323-5C>A	splice_region intron	N/A	ENSP00000432046.3
DNAAF3	ENST00000455045.5	TSL:1	c.161-5C>A	splice_region intron	N/A	ENSP00000394343.1
DNAAF3	ENST00000528412.5	TSL:1	n.*111-5C>A	splice_region intron	N/A	ENSP00000433826.2

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150726

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1097556

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

518262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23026

American (AMR)

AF:

0.00

AC:

AN:

8596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14380

East Asian (EAS)

AF:

0.00

AC:

AN:

26524

South Asian (SAS)

AF:

0.00

AC:

AN:

19692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4348

European-Non Finnish (NFE)

AF:

0.0000163

AC:

AN:

920622

Other (OTH)

AF:

0.00

AC:

AN:

43934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

150726

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40012

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2080

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

-0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: -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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over