chrX-111401162-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3PP5_Moderate
The NM_001195553.2(DCX):c.533G>A(p.Arg178His) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,209,345 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001195553.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DCX | ENST00000636035.2 | c.533G>A | p.Arg178His | missense_variant | Exon 3 of 7 | 2 | NM_001195553.2 | ENSP00000490614.1 | ||
DCX | ENST00000356220.8 | c.533G>A | p.Arg178His | missense_variant | Exon 4 of 8 | 5 | ENSP00000348553.4 | |||
DCX | ENST00000637453.1 | c.533G>A | p.Arg178His | missense_variant | Exon 3 of 7 | 5 | ENSP00000490357.1 | |||
DCX | ENST00000637570.1 | c.533G>A | p.Arg178His | missense_variant | Exon 3 of 7 | 5 | ENSP00000490878.1 |
Frequencies
GnomAD3 genomes AF: 0.0000180 AC: 2AN: 111241Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33435
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1098104Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 363546
GnomAD4 genome AF: 0.0000180 AC: 2AN: 111241Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33435
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Apparently de novo variant in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23365099) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at