16-84145457-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178452.6(DNAAF1):c.17C>T(p.Ser6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,579,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0660

Publications

0 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055501223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.17C>T	p.Ser6Leu	missense_variant	Exon 1 of 12	ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAAF1	ENST00000378553.10 link	c.17C>T	p.Ser6Leu	missense_variant	Exon 1 of 12	1	NM_178452.6	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000567918.5 link	n.17C>T		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000455154.1	H3BP51
DNAAF1	ENST00000563093.5 link	n.17C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000457373.1	Q8NEP3-3
DNAAF1	ENST00000570298.5 link	n.171C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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

GnomAD2 exomes

AF:

0.00000519

AC:

AN:

192672

AF XY:

0.00000971

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1427358

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

706562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33144

American (AMR)

AF:

0.00

AC:

AN:

38622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25324

East Asian (EAS)

AF:

0.00

AC:

AN:

38484

South Asian (SAS)

AF:

0.00

AC:

AN:

81256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1095296

Other (OTH)

AF:

0.00

AC:

AN:

59172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.17C>T (p.S6L) alteration is located in exon 1 (coding exon 1) of the DNAAF1 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0037

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.73

M_CAP

Benign

0.0053

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.066

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.0

REVEL

Benign

0.027

Sift

Benign

0.21

Sift4G

Uncertain

0.059

Polyphen

0.054

Vest4

0.057

MutPred

0.18

Loss of glycosylation at S6 (P = 0.0076);

MVP

0.20

MPC

0.020

ClinPred

0.091

GERP RS

1.2

PromoterAI

0.023

Neutral

(source)

Varity_R

0.093

gMVP

0.18

Mutation Taster

=97/3

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

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

16-84145457-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over