rs1556200641
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP2PP3_StrongPP5
The NM_001079872.2(CUL4B):c.1786C>T(p.Arg596Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R596L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001079872.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.1786C>T | p.Arg596Cys | missense_variant | 13/20 | ENST00000371322.11 | |
CUL4B | NM_003588.4 | c.1840C>T | p.Arg614Cys | missense_variant | 15/22 | ||
CUL4B | NM_001330624.2 | c.1801C>T | p.Arg601Cys | missense_variant | 14/21 | ||
CUL4B | NM_001369145.1 | c.1252C>T | p.Arg418Cys | missense_variant | 13/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.1786C>T | p.Arg596Cys | missense_variant | 13/20 | 1 | NM_001079872.2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 28
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
X-linked intellectual disability Cabezas type Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | - | This variant has not been previously reported or functionally characterized in the literature to our knowledge. The CUL4B gene is constrained against variation (Z-score= 3.77 and pLI = 1), and missense variants are a common mechanism of disease (PMID: 25385192, 17236139). The c.1840C>T (p.Arg614Cys) variant is absent from the gnomAD population database and thus is presumed to be rare. The c.1840C>T (p.Arg614Cys) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.1840C>T (p.Arg614Cys) variant is classified as Likely Pathogenic. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 28, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at