chr15-55430708-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_130810.4(DNAAF4):c.1225A>T(p.Ile409Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I409I) has been classified as Likely benign.
Frequency
Consequence
NM_130810.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.1225A>T | p.Ile409Phe | missense_variant | 10/10 | ENST00000321149.7 | |
DNAAF4-CCPG1 | NR_037923.1 | n.1408+1789A>T | intron_variant, non_coding_transcript_variant | ||||
DNAAF4 | NM_001033559.3 | c.1119A>T | p.Arg373Ser | missense_variant | 9/9 | ||
DNAAF4 | NM_001033560.2 | c.1047+4197A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF4 | ENST00000321149.7 | c.1225A>T | p.Ile409Phe | missense_variant | 10/10 | 1 | NM_130810.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251284Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135830
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461106Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726876
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 22, 2016 | In summary, this variant is a novel missense change with uncertain impact on protein function. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DYX1C1-related disease. This sequence change replaces isoleucine with phenylalanine at codon 409 of the DYX1C1 protein (p.Ile409Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at