rs770403610
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001256715.2(DNAAF3):c.350G>A(p.Trp117Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,250,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001256715.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF3 | NM_001256715.2 | c.350G>A | p.Trp117Ter | stop_gained | 5/12 | ENST00000524407.7 | |
DNAAF3-AS1 | XR_007067344.1 | n.307-489C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF3 | ENST00000524407.7 | c.350G>A | p.Trp117Ter | stop_gained | 5/12 | 1 | NM_001256715.2 | A2 | |
DNAAF3-AS1 | ENST00000591665.1 | n.1137-489C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000155 AC: 17AN: 1098392Hom.: 0 Cov.: 31 AF XY: 0.0000173 AC XY: 9AN XY: 518756
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74376
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change creates a premature translational stop signal (p.Trp185*) in the DNAAF3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAAF3 are known to be pathogenic (PMID: 22387996). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with DNAAF3-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 572342). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at