chr16-84170068-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178452.6(DNAAF1):c.1240G>C(p.Gly414Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G414V) has been classified as Uncertain significance.
Frequency
Consequence
NM_178452.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.1240G>C | p.Gly414Arg | missense_variant | 8/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.1240G>C | p.Gly414Arg | missense_variant | 8/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000563818.5 | n.917G>C | non_coding_transcript_exon_variant | 4/8 | 2 | ||||
DNAAF1 | ENST00000570298.5 | n.1394G>C | non_coding_transcript_exon_variant | 8/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.1225+15G>C | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 94
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2017 | In summary, this variant has uncertain impact on DNAAF1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a DNAAF1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 414 of the DNAAF1 protein (p.Gly414Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at