chr19-55161777-C-T

Position:

chr19-55161777-C-T

Variant summary

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

The NM_001256715.2(DNAAF3):c.529G>A(p.Gly177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,500,488 control chromosomes in the GnomAD database, including 4,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 741 hom., cov: 32)

Exomes 𝑓: 0.046 ( 4135 hom. )

Consequence

DNAAF3
NM_001256715.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0640

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048737824).

BP6

Variant 19-55161777-C-T is Benign according to our data. Variant chr19-55161777-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.529G>A	p.Gly177Ser	missense_variant	6/12	ENST00000524407.7	NP_001243644.1
DNAAF3-AS1	XR_007067344.1 linkuse as main transcript	n.306+563C>T		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.529G>A	p.Gly177Ser	missense_variant	6/12	1	NM_001256715.2	ENSP00000432046	A2	Q8N9W5-1
DNAAF3-AS1	ENST00000591665.1 linkuse as main transcript	n.1136+563C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9397

AN:

152182

Hom.:

730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0721

GnomAD3 exomes

AF:

0.120

AC:

12739

AN:

106158

Hom.:

1733

AF XY:

0.109

AC XY:

6304

AN XY:

57658

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.216

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.0457

AC:

61651

AN:

1348188

Hom.:

4135

Cov.:

AF XY:

0.0469

AC XY:

30994

AN XY:

661510

show subpopulations

Gnomad4 AFR exome

AF:

0.0490

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0563

GnomAD4 genome

AF:

0.0619

AC:

9430

AN:

152300

Hom.:

741

Cov.:

AF XY:

0.0664

AC XY:

4944

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0268

Gnomad4 OTH

AF:

0.0728

Alfa

AF:

0.0406

Hom.:

372

Bravo

AF:

0.0770

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.0370

AC:

136

ESP6500EA

AF:

0.0234

AC:

184

ExAC

AF:

0.0479

AC:

4867

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 22, 2016	- -

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 15, 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. -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
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

- -

Familial restrictive cardiomyopathy

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.5

DANN

Benign

0.91

DEOGEN2

Benign

0.00061

.;T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

.;M;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.63

N;.;.;N

REVEL

Benign

0.046

Sift

Benign

0.61

T;.;.;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.62

.;P;.;.

Vest4

0.083

MPC

1.5

ClinPred

0.0065

GERP RS

2.5

Varity_R

0.035

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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