rs199882635
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM4BS1_Supporting
The ENST00000524407.7(DNAAF3):āc.1626A>Gā(p.Ter542TrpextTer4) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,578,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
ENST00000524407.7 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF3 | NM_001256715.2 | c.1626A>G | p.Ter542TrpextTer4 | stop_lost | 12/12 | ENST00000524407.7 | NP_001243644.1 | |
DNAAF3 | NM_001256714.1 | c.1827A>G | p.Ter609TrpextTer4 | stop_lost | 12/12 | NP_001243643.1 | ||
DNAAF3 | NM_178837.4 | c.1767A>G | p.Ter589TrpextTer4 | stop_lost | 12/12 | NP_849159.2 | ||
DNAAF3 | NM_001256716.2 | c.1464A>G | p.Ter488TrpextTer4 | stop_lost | 12/12 | NP_001243645.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF3 | ENST00000524407.7 | c.1626A>G | p.Ter542TrpextTer4 | stop_lost | 12/12 | 1 | NM_001256715.2 | ENSP00000432046 | A2 | |
DNAAF3-AS1 | ENST00000591665.1 | n.124T>C | non_coding_transcript_exon_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000482 AC: 73AN: 151548Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000137 AC: 31AN: 225952Hom.: 0 AF XY: 0.000105 AC XY: 13AN XY: 123432
GnomAD4 exome AF: 0.0000434 AC: 62AN: 1427110Hom.: 0 Cov.: 31 AF XY: 0.0000453 AC XY: 32AN XY: 706236
GnomAD4 genome AF: 0.000481 AC: 73AN: 151668Hom.: 0 Cov.: 33 AF XY: 0.000580 AC XY: 43AN XY: 74100
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 31, 2021 | - - |
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 14, 2022 | This sequence change disrupts the translational stop signal of the DNAAF3 mRNA. It is expected to extend the length of the DNAAF3 protein by 4 additional amino acid residues. This variant is present in population databases (rs199882635, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DNAAF3-related conditions. ClinVar contains an entry for this variant (Variation ID: 454620). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2024 | Normal stop codon changed to a Tryptophan codon, leading to the addition of 4 amino acids at the C-terminus; Has not been previously published as pathogenic or benign to our knowledge - |
DNAAF3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 05, 2023 | The DNAAF3 c.1827A>G variant is predicted to result in extension of the open reading frame (p.*609Trpext*4). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.16% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-55670430-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at