X-120530105-TACTGGAAATTTCA-T
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_2588delTGAAATTTCCAGT(p.Leu859fs) 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 0 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUL4B | NM_001079872.2 | c.2576_2588delTGAAATTTCCAGT | p.Leu859fs | frameshift_variant | Exon 19 of 20 | ENST00000371322.11 | NP_001073341.1 | |
CUL4B | NM_003588.4 | c.2630_2642delTGAAATTTCCAGT | p.Leu877fs | frameshift_variant | Exon 21 of 22 | NP_003579.3 | ||
CUL4B | NM_001330624.2 | c.2591_2603delTGAAATTTCCAGT | p.Leu864fs | frameshift_variant | Exon 20 of 21 | NP_001317553.1 | ||
CUL4B | NM_001369145.1 | c.2042_2054delTGAAATTTCCAGT | p.Leu681fs | frameshift_variant | Exon 19 of 20 | NP_001356074.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUL4B | ENST00000371322.11 | c.2576_2588delTGAAATTTCCAGT | p.Leu859fs | frameshift_variant | Exon 19 of 20 | 1 | NM_001079872.2 | ENSP00000360373.5 | ||
CUL4B | ENST00000681206.1 | c.2690_2702delTGAAATTTCCAGT | p.Leu897fs | frameshift_variant | Exon 22 of 23 | ENSP00000505480.1 | ||||
CUL4B | ENST00000680673.1 | c.2630_2642delTGAAATTTCCAGT | p.Leu877fs | frameshift_variant | Exon 21 of 22 | ENSP00000505084.1 | ||||
CUL4B | ENST00000681253.1 | c.2630_2642delTGAAATTTCCAGT | p.Leu877fs | frameshift_variant | Exon 22 of 23 | ENSP00000506259.1 | ||||
CUL4B | ENST00000681652.1 | c.2630_2642delTGAAATTTCCAGT | p.Leu877fs | frameshift_variant | Exon 24 of 25 | ENSP00000505176.1 | ||||
CUL4B | ENST00000336592.11 | c.2591_2603delTGAAATTTCCAGT | p.Leu864fs | frameshift_variant | Exon 20 of 21 | 5 | ENSP00000338919.6 | |||
CUL4B | ENST00000674137.11 | c.2582_2594delTGAAATTTCCAGT | p.Leu861fs | frameshift_variant | Exon 19 of 20 | ENSP00000501019.6 | ||||
CUL4B | ENST00000681090.1 | c.2483_2495delTGAAATTTCCAGT | p.Leu828fs | frameshift_variant | Exon 19 of 20 | ENSP00000506288.1 | ||||
CUL4B | ENST00000679927.1 | c.2231_2243delTGAAATTTCCAGT | p.Leu744fs | frameshift_variant | Exon 20 of 21 | ENSP00000505603.1 | ||||
CUL4B | ENST00000371323.3 | c.2042_2054delTGAAATTTCCAGT | p.Leu681fs | frameshift_variant | Exon 19 of 20 | 5 | ENSP00000360374.3 | |||
CUL4B | ENST00000680474.1 | c.2018_2030delTGAAATTTCCAGT | p.Leu673fs | frameshift_variant | Exon 18 of 20 | ENSP00000505562.1 | ||||
CUL4B | ENST00000679844.1 | c.1913_1925delTGAAATTTCCAGT | p.Leu638fs | frameshift_variant | Exon 17 of 18 | ENSP00000505239.1 | ||||
CUL4B | ENST00000404115.8 | c.2439+2304_2439+2316delTGAAATTTCCAGT | intron_variant | Intron 18 of 18 | 1 | ENSP00000384109.4 | ||||
CUL4B | ENST00000673919.1 | n.*2023_*2035delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 20 of 21 | ENSP00000500994.1 | |||||
CUL4B | ENST00000674073.2 | n.*132_*144delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 17 of 18 | ENSP00000501262.2 | |||||
CUL4B | ENST00000679405.1 | n.*1785_*1797delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 21 of 22 | ENSP00000504985.1 | |||||
CUL4B | ENST00000679432.1 | n.*1785_*1797delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 21 of 22 | ENSP00000505343.1 | |||||
CUL4B | ENST00000680918.1 | n.*1492_*1504delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 17 of 18 | ENSP00000505955.1 | |||||
CUL4B | ENST00000681080.1 | n.*1785_*1797delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505898.1 | |||||
CUL4B | ENST00000681189.1 | n.*742_*754delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505973.1 | |||||
CUL4B | ENST00000681333.1 | n.*3469_*3481delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 16 of 17 | ENSP00000505739.1 | |||||
CUL4B | ENST00000681908.1 | n.*748_*760delTGAAATTTCCAGT | non_coding_transcript_exon_variant | Exon 19 of 20 | ENSP00000505777.1 | |||||
CUL4B | ENST00000673919.1 | n.*2023_*2035delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 20 of 21 | ENSP00000500994.1 | |||||
CUL4B | ENST00000674073.2 | n.*132_*144delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 17 of 18 | ENSP00000501262.2 | |||||
CUL4B | ENST00000679405.1 | n.*1785_*1797delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 21 of 22 | ENSP00000504985.1 | |||||
CUL4B | ENST00000679432.1 | n.*1785_*1797delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 21 of 22 | ENSP00000505343.1 | |||||
CUL4B | ENST00000680918.1 | n.*1492_*1504delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 17 of 18 | ENSP00000505955.1 | |||||
CUL4B | ENST00000681080.1 | n.*1785_*1797delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505898.1 | |||||
CUL4B | ENST00000681189.1 | n.*742_*754delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505973.1 | |||||
CUL4B | ENST00000681333.1 | n.*3469_*3481delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 16 of 17 | ENSP00000505739.1 | |||||
CUL4B | ENST00000681908.1 | n.*748_*760delTGAAATTTCCAGT | 3_prime_UTR_variant | Exon 19 of 20 | ENSP00000505777.1 |
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
Oct 20, 2022
Eurofins-Biomnis
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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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.