rs4720951
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017802.4(DNAAF5):āc.1895T>Cā(p.Val632Ala) variant causes a missense change. The variant allele was found at a frequency of 0.454 in 1,613,284 control chromosomes in the GnomAD database, including 168,411 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.43 ( 14620 hom., cov: 34)
Exomes š: 0.46 ( 153791 hom. )
Consequence
DNAAF5
NM_017802.4 missense
NM_017802.4 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 3.94
Genes affected
DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.004177332).
BP6
Variant 7-770582-T-C is Benign according to our data. Variant chr7-770582-T-C is described in ClinVar as [Benign]. Clinvar id is 260930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.1895T>C | p.Val632Ala | missense_variant | 9/13 | ENST00000297440.11 | |
DNAAF5 | XM_024446813.2 | c.1895T>C | p.Val632Ala | missense_variant | 9/12 | ||
DNAAF5 | NR_075098.2 | n.1855T>C | non_coding_transcript_exon_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.1895T>C | p.Val632Ala | missense_variant | 9/13 | 1 | NM_017802.4 | P1 | |
DNAAF5 | ENST00000403952.3 | c.170T>C | p.Val57Ala | missense_variant | 2/6 | 1 | |||
DNAAF5 | ENST00000440747.5 | c.1301T>C | p.Val434Ala | missense_variant | 9/13 | 2 | |||
DNAAF5 | ENST00000491496.1 | n.180T>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.433 AC: 65803AN: 152002Hom.: 14599 Cov.: 34
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GnomAD3 exomes AF: 0.434 AC: 108814AN: 250670Hom.: 24037 AF XY: 0.434 AC XY: 58900AN XY: 135630
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GnomAD4 exome AF: 0.457 AC: 667023AN: 1461164Hom.: 153791 Cov.: 49 AF XY: 0.455 AC XY: 330459AN XY: 726926
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GnomAD4 genome AF: 0.433 AC: 65858AN: 152120Hom.: 14620 Cov.: 34 AF XY: 0.432 AC XY: 32165AN XY: 74390
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 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 | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 07, 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. - |
Primary ciliary dyskinesia 18 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at