rs56726774

Positions:

chr19-55161796-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000524407.7(DNAAF3):c.510A>G(p.Val170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,480,518 control chromosomes in the GnomAD database, including 4,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 774 hom., cov: 32)

Exomes 𝑓: 0.046 ( 4014 hom. )

Consequence

DNAAF3
ENST00000524407.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.0250

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 19-55161796-T-C is Benign according to our data. Variant chr19-55161796-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55161796-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.025 with no splicing effect.

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/exons	MANE	Protein	UniProt
DNAAF3	NM_001256715.2 linkuse as main transcript	c.510A>G	p.Val170=	synonymous_variant	6/12	ENST00000524407.7	NP_001243644.1
DNAAF3-AS1	XR_007067344.1 linkuse as main transcript	n.306+582T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7 linkuse as main transcript	c.510A>G	p.Val170=	synonymous_variant	6/12	1	NM_001256715.2	ENSP00000432046	A2	Q8N9W5-1
DNAAF3-AS1	ENST00000591665.1 linkuse as main transcript	n.1136+582T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0654

AC:

9959

AN:

152184

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0612

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0750

GnomAD3 exomes

AF:

0.126

AC:

11474

AN:

90960

Hom.:

1589

AF XY:

0.115

AC XY:

5596

AN XY:

48750

show subpopulations

Gnomad AFR exome

AF:

0.0641

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0373

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0851

GnomAD4 exome

AF:

0.0459

AC:

60955

AN:

1328216

Hom.:

4014

Cov.:

AF XY:

0.0470

AC XY:

30499

AN XY:

649138

show subpopulations

Gnomad4 AFR exome

AF:

0.0625

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0332

Gnomad4 NFE exome

AF:

0.0271

Gnomad4 OTH exome

AF:

0.0572

GnomAD4 genome

AF:

0.0656

AC:

9992

AN:

152302

Hom.:

774

Cov.:

AF XY:

0.0701

AC XY:

5218

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0612

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0756

Alfa

AF:

0.0412

Hom.:

Bravo

AF:

0.0809

Asia WGS

AF:

0.193

AC:

672

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 22, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 08, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Dilated Cardiomyopathy, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypertrophic cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial restrictive cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.6

DANN

Benign

0.45

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