chr16-84170053-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178452.6(DNAAF1):c.1225G>T(p.Gly409Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Synonymous variant affecting the same amino acid position (i.e. G409G) has been classified as Likely benign.
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.1225G>T | p.Gly409Cys | missense_variant | 8/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.1225G>T | p.Gly409Cys | missense_variant | 8/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000563818.5 | n.902G>T | non_coding_transcript_exon_variant | 4/8 | 2 | ||||
DNAAF1 | ENST00000570298.5 | n.1379G>T | non_coding_transcript_exon_variant | 8/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.1225G>T | p.Asp409Tyr | missense_variant, splice_region_variant, NMD_transcript_variant | 8/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251310Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135836
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461510Hom.: 0 Cov.: 94 AF XY: 0.00000138 AC XY: 1AN XY: 727078
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74384
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2017 | This sequence change replaces glycine with cysteine at codon 409 of the DNAAF1 protein (p.Gly409Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DNAAF1-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at