rs530669133
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_130810.4(DNAAF4):c.697C>T(p.Arg233Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,976 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. R233H) has been classified as Uncertain significance.
Frequency
Consequence
NM_130810.4 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 |
---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.697C>T | p.Arg233Cys | missense_variant | 6/10 | ENST00000321149.7 | |
DNAAF4-CCPG1 | NR_037923.1 | n.952C>T | non_coding_transcript_exon_variant | 5/16 | |||
DNAAF4 | NM_001033560.2 | c.697C>T | p.Arg233Cys | missense_variant | 6/9 | ||
DNAAF4 | NM_001033559.3 | c.697C>T | p.Arg233Cys | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF4 | ENST00000321149.7 | c.697C>T | p.Arg233Cys | missense_variant | 6/10 | 1 | NM_130810.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251170Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135726
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461706Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727116
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74454
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 14, 2018 | This sequence change replaces arginine with cysteine at codon 233 of the DYX1C1 protein (p.Arg233Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs530669133, ExAC 0.009%). This variant has not been reported in the literature in individuals with DYX1C1-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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