rs58824375

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

2
16

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-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

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
DNAAF3NM_001256715.2 linkuse as main transcriptc.529G>A p.Gly177Ser missense_variant 6/12 ENST00000524407.7 NP_001243644.1
DNAAF3-AS1XR_007067344.1 linkuse as main transcriptn.306+563C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAAF3ENST00000524407.7 linkuse as main transcriptc.529G>A p.Gly177Ser missense_variant 6/121 NM_001256715.2 ENSP00000432046 A2Q8N9W5-1
DNAAF3-AS1ENST00000591665.1 linkuse as main transcriptn.1136+563C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0617
AC:
9397
AN:
152182
Hom.:
730
Cov.:
32
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.:
33
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.:
32
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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Mar 22, 2016- -
Primary ciliary dyskinesia Benign:3
Benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 15, 2016This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJul 05, 2018- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Dilated Cardiomyopathy, Recessive Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Familial restrictive cardiomyopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.67
T
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
N
LIST_S2
Benign
0.57
T;T;T;T
MetaRNN
Benign
0.0049
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.2
.;M;.;.
MutationTaster
Benign
1.0
P;P;P;P;P;P;P
PrimateAI
Uncertain
0.61
T
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
T
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.

Other links and lift over

dbSNP: rs58824375; hg19: chr19-55673145; COSMIC: COSV61279013; COSMIC: COSV61279013; API