16-84145472-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_178452.6(DNAAF1):c.32G>C(p.Gly11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. G11G) has been classified as Likely benign.
Frequency
Consequence
NM_178452.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.32G>C | p.Gly11Ala | missense_variant | 1/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.32G>C | p.Gly11Ala | missense_variant | 1/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000567918.5 | c.32G>C | p.Gly11Ala | missense_variant, NMD_transcript_variant | 1/7 | 1 | |||
DNAAF1 | ENST00000570298.5 | n.186G>C | non_coding_transcript_exon_variant | 1/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.32G>C | p.Gly11Ala | missense_variant, NMD_transcript_variant | 1/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1425784Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1AN XY: 705522
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 10, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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). This sequence change replaces glycine with alanine at codon 11 of the DNAAF1 protein (p.Gly11Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at