15-55430733-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_130810.4(DNAAF4):c.1200A>T(p.Lys400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_130810.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.1200A>T | p.Lys400Asn | missense_variant | Exon 10 of 10 | ENST00000321149.7 | NP_570722.2 | |
DNAAF4 | NM_001033559.3 | c.1094A>T | p.Lys365Ile | missense_variant | Exon 9 of 9 | NP_001028731.1 | ||
DNAAF4 | NM_001033560.2 | c.1047+4172A>T | intron_variant | Intron 8 of 8 | NP_001028732.1 | |||
DNAAF4-CCPG1 | NR_037923.1 | n.1408+1764A>T | intron_variant | Intron 8 of 15 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251316Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135846
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461200Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726934
GnomAD4 genome AF: 0.000164 AC: 25AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2025 | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 400 of the DNAAF4 protein (p.Lys400Asn). This variant is present in population databases (rs143213850, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with DNAAF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018752). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DNAAF4 protein function with a negative predictive value of 80%. 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