rs1461569802

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256715.2(DNAAF3):​c.730G>T​(p.Asp244Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

DNAAF3
NM_001256715.2 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAAF3NM_001256715.2 linkuse as main transcriptc.730G>T p.Asp244Tyr missense_variant 7/12 ENST00000524407.7 NP_001243644.1 Q8N9W5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAAF3ENST00000524407.7 linkuse as main transcriptc.730G>T p.Asp244Tyr missense_variant 7/121 NM_001256715.2 ENSP00000432046.3 Q8N9W5-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 12, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 525449). This missense change has been observed in individual(s) with primary ciliary dyskinesia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 312 of the DNAAF3 protein (p.Asp312Tyr). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
35
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
.;T;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.82
T;T;T;T
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.74
D;D;D;D
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.5
.;M;.;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-5.0
D;.;.;D
REVEL
Benign
0.27
Sift
Uncertain
0.0020
D;.;.;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.83
MutPred
0.46
.;Gain of sheet (P = 0.0344);.;.;
MVP
0.53
MPC
0.95
ClinPred
0.99
D
GERP RS
4.2
Varity_R
0.54
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.97
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.97
Position offset: 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: rs1461569802; hg19: chr19-55672720; API