rs1555521110
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_178452.6(DNAAF1):c.471_473del(p.Phe157del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DNAAF1
NM_178452.6 inframe_deletion
NM_178452.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.60
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_178452.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.471_473del | p.Phe157del | inframe_deletion | 4/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.471_473del | p.Phe157del | inframe_deletion | 4/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000567918.5 | c.471_473del | p.Phe157del | inframe_deletion, NMD_transcript_variant | 4/7 | 1 | |||
DNAAF1 | ENST00000570298.5 | n.625_627del | non_coding_transcript_exon_variant | 4/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.471_473del | p.Phe157del | inframe_deletion, NMD_transcript_variant | 4/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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 submitter | clinical testing | Invitae | May 03, 2017 | In summary, this variant is a rare in-frame deletion with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. This variant occurs with a second rare variant (p.Asn109Lys) in DNAAF1 in an individual with primary ciliary dyskinesia (Invitae). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests the c.471_473delCTT substitution may contribute to the cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change deletes 3 nucleotides from exon 4 of the DNAAF1 mRNA (c.471_473delCTT). This leads to the deletion of 1 amino acid residue in the DNAAF1 protein (p.Phe157del) but otherwise preserves the integrity of the reading frame. - |
Computational scores
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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