rs73036225
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_017802.4(DNAAF5):c.1269C>T(p.Ser423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,080 control chromosomes in the GnomAD database, including 33,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.14 ( 2135 hom., cov: 33)
Exomes 𝑓: 0.20 ( 31446 hom. )
Consequence
DNAAF5
NM_017802.4 synonymous
NM_017802.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.22
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 7-756793-C-T is Benign according to our data. Variant chr7-756793-C-T is described in ClinVar as [Benign]. Clinvar id is 260925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-756793-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.22 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.1269C>T | p.Ser423= | synonymous_variant | 6/13 | ENST00000297440.11 | |
DNAAF5 | XM_024446813.2 | c.1269C>T | p.Ser423= | synonymous_variant | 6/12 | ||
DNAAF5 | NR_075098.2 | n.1229C>T | non_coding_transcript_exon_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.1269C>T | p.Ser423= | synonymous_variant | 6/13 | 1 | NM_017802.4 | P1 | |
DNAAF5 | ENST00000440747.5 | c.675C>T | p.Ser225= | synonymous_variant | 6/13 | 2 | |||
DNAAF5 | ENST00000437419.5 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.144 AC: 21894AN: 152152Hom.: 2138 Cov.: 33
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GnomAD3 exomes AF: 0.162 AC: 40769AN: 251052Hom.: 4116 AF XY: 0.172 AC XY: 23319AN XY: 135792
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GnomAD4 exome AF: 0.200 AC: 292268AN: 1460810Hom.: 31446 Cov.: 34 AF XY: 0.201 AC XY: 146049AN XY: 726718
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GnomAD4 genome ? AF: 0.144 AC: 21888AN: 152270Hom.: 2135 Cov.: 33 AF XY: 0.139 AC XY: 10364AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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