Genetic Variant DNAAF1:c.-83dupT (chr16-84145357-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_178452.6(DNAAF1):c.-83dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,541,052 control chromosomes in the GnomAD database, including 1,079 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.048 ( 336 hom., cov: 31)

Exomes 𝑓: 0.027 ( 743 hom. )

Consequence

DNAAF1
NM_178452.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.72

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 links:

HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HSDL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 16-84145357-C-CT is Benign according to our data. Variant chr16-84145357-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 320764.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.-83dupT		5_prime_UTR_variant	Exon 1 of 12	ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4
HSDL1	NM_031463.5 link	c.-347dupA		upstream_gene_variant		ENST00000219439.9	NP_113651.4	Q3SXM5-1I6L975

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 link	c.-83dupT		5_prime_UTR_variant	Exon 1 of 12	1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1
HSDL1	ENST00000219439.9 link	c.-347dupA		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4		Q3SXM5-1

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

7326

AN:

151906

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0450

GnomAD4 exome

AF:

0.0271

AC:

37623

AN:

1389028

Hom.:

743

Cov.:

AF XY:

0.0276

AC XY:

18897

AN XY:

685564

show subpopulations

African (AFR)

AF:

0.118

AC:

3741

AN:

31604

American (AMR)

AF:

0.0221

AC:

787

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

661

AN:

25126

East Asian (EAS)

AF:

0.000167

AC:

AN:

35856

South Asian (SAS)

AF:

0.0473

AC:

3741

AN:

79138

European-Finnish (FIN)

AF:

0.00600

AC:

248

AN:

41352

Middle Eastern (MID)

AF:

0.0678

AC:

362

AN:

5336

European-Non Finnish (NFE)

AF:

0.0243

AC:

26176

AN:

1077144

Other (OTH)

AF:

0.0329

AC:

1901

AN:

57794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1953

3907

5860

7814

9767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0483

AC:

7344

AN:

152024

Hom.:

336

Cov.:

AF XY:

0.0468

AC XY:

3479

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.116

AC:

4820

AN:

41466

American (AMR)

AF:

0.0316

AC:

483

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.0393

AC:

189

AN:

4814

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0233

AC:

1584

AN:

67924

Other (OTH)

AF:

0.0440

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

351

702

1053

1404

1755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0353

Hom.:

Bravo

AF:

0.0524

Asia WGS

AF:

0.0270

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Mutation Taster

=300/0

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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16-84145357-C-CT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over