chr16-84150322-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178452.6(DNAAF1):c.332C>T(p.Thr111Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,752 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T111K) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.332C>T | p.Thr111Met | missense_variant | Exon 3 of 12 | ENST00000378553.10 | NP_848547.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.332C>T | p.Thr111Met | missense_variant | Exon 3 of 12 | 1 | NM_178452.6 | ENSP00000367815.5 | ||
DNAAF1 | ENST00000567918.5 | n.332C>T | non_coding_transcript_exon_variant | Exon 3 of 7 | 1 | ENSP00000455154.1 | ||||
DNAAF1 | ENST00000563093.5 | n.332C>T | non_coding_transcript_exon_variant | Exon 3 of 11 | 2 | ENSP00000457373.1 | ||||
DNAAF1 | ENST00000570298.5 | n.486C>T | non_coding_transcript_exon_variant | Exon 3 of 11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251350Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135850
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460592Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726694
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 111 of the DNAAF1 protein (p.Thr111Met). This variant is present in population databases (rs375812500, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DNAAF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 568488). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at