NM_178452.6:c.7C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178452.6(DNAAF1):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,428,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DNAAF1
NM_178452.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18550214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.7C>T	p.Pro3Ser	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.7C>T	p.Pro3Ser	missense_variant	Exon 1 of 12	1	NM_178452.6	ENSP00000367815.5	Q8NEP3-1
DNAAF1	ENST00000567918.5 link	n.7C>T		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000455154.1	H3BP51
DNAAF1	ENST00000563093.5 link	n.7C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000457373.1	Q8NEP3-3
DNAAF1	ENST00000570298.5 link	n.161C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000511

AC:

AN:

195606

AF XY:

0.00000956

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1428642

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

707282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33160

American (AMR)

AF:

0.00

AC:

AN:

38904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25338

East Asian (EAS)

AF:

0.00

AC:

AN:

38516

South Asian (SAS)

AF:

0.0000492

AC:

AN:

81348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096002

Other (OTH)

AF:

0.00

AC:

AN:

59220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Nov 09, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.7C>T (p.P3S) 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 7, causing the proline (P) at amino acid position 3 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

-0.0041

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.74

M_CAP

Benign

0.019

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

PhyloP100

1.2

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.088

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.52

Vest4

0.30

MutPred

0.15

Gain of phosphorylation at P3 (P = 0.0117);

MVP

0.56

MPC

0.16

ClinPred

0.94

GERP RS

3.4

PromoterAI

0.012

Neutral

(source)

Varity_R

0.20

gMVP

0.47

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_178452.6:c.7C>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