NM_001256715.2:c.1001T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256715.2(DNAAF3):c.1001T>C(p.Leu334Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,613,638 control chromosomes in the GnomAD database, including 6,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 716 hom., cov: 32)

Exomes 𝑓: 0.048 ( 5484 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.170

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:

ENSG00000267110 (HGNC:):

ENSG00000267110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004614681).

BP6

Variant 19-55160687-A-G is Benign according to our data. Variant chr19-55160687-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55160687-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 link	c.1001T>C	p.Leu334Pro	missense_variant	Exon 9 of 12	ENST00000524407.7	NP_001243644.1	Q8N9W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 link	c.1001T>C	p.Leu334Pro	missense_variant	Exon 9 of 12	1	NM_001256715.2	ENSP00000432046.3		Q8N9W5-1
ENSG00000267110	ENST00000587871.1 link	n.-17T>C		upstream_gene_variant		5		ENSP00000473050.1		M0R381

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9217

AN:

152094

Hom.:

706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0214

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.0883

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0680

GnomAD3 exomes

AF:

0.0979

AC:

24271

AN:

248004

Hom.:

3348

AF XY:

0.0855

AC XY:

11519

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.0506

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.0847

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0478

AC:

69810

AN:

1461426

Hom.:

5484

Cov.:

AF XY:

0.0472

AC XY:

34326

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.0214

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.0832

Gnomad4 FIN exome

AF:

0.0319

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0542

GnomAD4 genome

AF:

0.0608

AC:

9249

AN:

152212

Hom.:

716

Cov.:

AF XY:

0.0645

AC XY:

4799

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0504

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.0214

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0266

Gnomad4 OTH

AF:

0.0678

Alfa

AF:

0.0456

Hom.:

535

Bravo

AF:

0.0772

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0288

AC:

111

ESP6500AA

AF:

0.0394

AC:

152

ESP6500EA

AF:

0.0213

AC:

176

ExAC

AF:

0.0859

AC:

10383

Asia WGS

AF:

0.156

AC:

544

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated Cardiomyopathy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial restrictive cardiomyopathy

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

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.8

DANN

Benign

0.71

DEOGEN2

Benign

0.00055

.;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

.;N;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

2.4

N;.;.;N

REVEL

Benign

0.28

Sift

Benign

0.34

T;.;.;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.035

MPC

0.36

ClinPred

0.0080

GERP RS

1.5

Varity_R

0.066

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over