rs375812500
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178452.6(DNAAF1):c.332C>A(p.Thr111Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,460,592 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. T111M) 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF1 | NM_178452.6 | c.332C>A | p.Thr111Lys | missense_variant | 3/12 | ENST00000378553.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF1 | ENST00000378553.10 | c.332C>A | p.Thr111Lys | missense_variant | 3/12 | 1 | NM_178452.6 | P1 | |
DNAAF1 | ENST00000567918.5 | c.332C>A | p.Thr111Lys | missense_variant, NMD_transcript_variant | 3/7 | 1 | |||
DNAAF1 | ENST00000570298.5 | n.486C>A | non_coding_transcript_exon_variant | 3/11 | 2 | ||||
DNAAF1 | ENST00000563093.5 | c.332C>A | p.Thr111Lys | missense_variant, NMD_transcript_variant | 3/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251350Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135850
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460592Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726694
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2022 | The c.332C>A (p.T111K) alteration is located in exon 3 (coding exon 3) of the DNAAF1 gene. This alteration results from a C to A substitution at nucleotide position 332, causing the threonine (T) at amino acid position 111 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2022 | This variant has not been reported in the literature in individuals affected with DNAAF1-related conditions. This variant is present in population databases (rs375812500, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 111 of the DNAAF1 protein (p.Thr111Lys). ClinVar contains an entry for this variant (Variation ID: 641500). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at