Genetic Variant NM_001256715.2:c.*28A>C (chr19-55159034-T-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001256715.2(DNAAF3):c.*28A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,536,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

DNAAF3
NM_001256715.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.83

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:

ENSG00000267110 (HGNC:):

ENSG00000267110 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000496 (687/1384478) while in subpopulation NFE AF = 0.000566 (609/1076138). AF 95% confidence interval is 0.000529. There are 0 homozygotes in GnomAdExome4. There are 342 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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	UniProt
DNAAF3	NM_001256715.2	MANE Select	c.*28A>C	3_prime_UTR	Exon 12 of 12	NP_001243644.1	Q8N9W5-1
DNAAF3	NM_001256714.1		c.*28A>C	3_prime_UTR	Exon 12 of 12	NP_001243643.1	Q8N9W5-3
DNAAF3	NM_178837.4		c.*28A>C	3_prime_UTR	Exon 12 of 12	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.*28A>C	3_prime_UTR	Exon 12 of 12	ENSP00000432046.3	Q8N9W5-1
DNAAF3	ENST00000455045.5	TSL:1	c.*28A>C	3_prime_UTR	Exon 12 of 12	ENSP00000394343.1	Q8N9W5-7
DNAAF3	ENST00000528412.5	TSL:1	n.*1442A>C	non_coding_transcript_exon	Exon 12 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000174

AC:

AN:

189600

AF XY:

0.000195

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000439

Gnomad ASJ exome

AF:

0.000857

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000496

AC:

687

AN:

1384478

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

342

AN XY:

681452

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30630

American (AMR)

AF:

0.0000635

AC:

AN:

31482

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

21140

East Asian (EAS)

AF:

0.00

AC:

AN:

38974

South Asian (SAS)

AF:

0.000255

AC:

AN:

74492

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5288

European-Non Finnish (NFE)

AF:

0.000566

AC:

609

AN:

1076138

Other (OTH)

AF:

0.000545

AC:

AN:

56908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000283

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41512

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.000310

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.68

(source)

DANN

Benign

0.69

PhyloP100

-2.8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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