chrX-120530105-TACTGGAAATTTCA-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001079872.2(CUL4B):c.2576_2588del(p.Leu859Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
CUL4B
NM_001079872.2 frameshift
NM_001079872.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
CUL4B (HGNC:2555): (cullin 4B) This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0417 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-120530105-TACTGGAAATTTCA-T is Pathogenic according to our data. Variant chrX-120530105-TACTGGAAATTTCA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2506462.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.2576_2588del | p.Leu859Ter | frameshift_variant | 19/20 | ENST00000371322.11 | |
CUL4B | NM_001330624.2 | c.2591_2603del | p.Leu864Ter | frameshift_variant | 20/21 | ||
CUL4B | NM_001369145.1 | c.2042_2054del | p.Leu681Ter | frameshift_variant | 19/20 | ||
CUL4B | NM_003588.4 | c.2630_2642del | p.Leu877Ter | frameshift_variant | 21/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.2576_2588del | p.Leu859Ter | frameshift_variant | 19/20 | 1 | NM_001079872.2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked intellectual disability Cabezas type Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Eurofins-Biomnis | Oct 20, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.