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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.60
Variant links:
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
CUL4BNM_001079872.2 linkc.2576_2588delTGAAATTTCCAGT p.Leu859fs frameshift_variant Exon 19 of 20 ENST00000371322.11 NP_001073341.1 Q13620-1
CUL4BNM_003588.4 linkc.2630_2642delTGAAATTTCCAGT p.Leu877fs frameshift_variant Exon 21 of 22 NP_003579.3 Q13620-2
CUL4BNM_001330624.2 linkc.2591_2603delTGAAATTTCCAGT p.Leu864fs frameshift_variant Exon 20 of 21 NP_001317553.1 K4DI93
CUL4BNM_001369145.1 linkc.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
CUL4BENST00000371322.11 linkc.2576_2588delTGAAATTTCCAGT p.Leu859fs frameshift_variant Exon 19 of 20 1 NM_001079872.2 ENSP00000360373.5 Q13620-1
CUL4BENST00000681206.1 linkc.2690_2702delTGAAATTTCCAGT p.Leu897fs frameshift_variant Exon 22 of 23 ENSP00000505480.1 A0A7P0T954
CUL4BENST00000680673.1 linkc.2630_2642delTGAAATTTCCAGT p.Leu877fs frameshift_variant Exon 21 of 22 ENSP00000505084.1 Q13620-2
CUL4BENST00000681253.1 linkc.2630_2642delTGAAATTTCCAGT p.Leu877fs frameshift_variant Exon 22 of 23 ENSP00000506259.1 Q13620-2
CUL4BENST00000681652.1 linkc.2630_2642delTGAAATTTCCAGT p.Leu877fs frameshift_variant Exon 24 of 25 ENSP00000505176.1 Q13620-2
CUL4BENST00000336592.11 linkc.2591_2603delTGAAATTTCCAGT p.Leu864fs frameshift_variant Exon 20 of 21 5 ENSP00000338919.6 K4DI93
CUL4BENST00000674137.11 linkc.2582_2594delTGAAATTTCCAGT p.Leu861fs frameshift_variant Exon 19 of 20 ENSP00000501019.6 A0A669KAX4
CUL4BENST00000681090.1 linkc.2483_2495delTGAAATTTCCAGT p.Leu828fs frameshift_variant Exon 19 of 20 ENSP00000506288.1 A0A7P0TAQ3
CUL4BENST00000679927.1 linkc.2231_2243delTGAAATTTCCAGT p.Leu744fs frameshift_variant Exon 20 of 21 ENSP00000505603.1 A0A7P0T9L3
CUL4BENST00000371323.3 linkc.2042_2054delTGAAATTTCCAGT p.Leu681fs frameshift_variant Exon 19 of 20 5 ENSP00000360374.3 Q13620-3
CUL4BENST00000680474.1 linkc.2018_2030delTGAAATTTCCAGT p.Leu673fs frameshift_variant Exon 18 of 20 ENSP00000505562.1 A0A7P0T9C8
CUL4BENST00000679844.1 linkc.1913_1925delTGAAATTTCCAGT p.Leu638fs frameshift_variant Exon 17 of 18 ENSP00000505239.1 A0A7P0T8P8
CUL4BENST00000404115.8 linkc.2439+2304_2439+2316delTGAAATTTCCAGT intron_variant Intron 18 of 18 1 ENSP00000384109.4 A0A804CL36
CUL4BENST00000673919.1 linkn.*2023_*2035delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 20 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*132_*144delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 17 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1785_*1797delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 21 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1785_*1797delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 21 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1492_*1504delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 17 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1785_*1797delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 19 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*742_*754delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 19 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3469_*3481delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 16 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*748_*760delTGAAATTTCCAGT non_coding_transcript_exon_variant Exon 19 of 20 ENSP00000505777.1 A0A7P0T9P5
CUL4BENST00000673919.1 linkn.*2023_*2035delTGAAATTTCCAGT 3_prime_UTR_variant Exon 20 of 21 ENSP00000500994.1 A0A669KAU9
CUL4BENST00000674073.2 linkn.*132_*144delTGAAATTTCCAGT 3_prime_UTR_variant Exon 17 of 18 ENSP00000501262.2 A0A669KBG9
CUL4BENST00000679405.1 linkn.*1785_*1797delTGAAATTTCCAGT 3_prime_UTR_variant Exon 21 of 22 ENSP00000504985.1 A0A7P0Z439
CUL4BENST00000679432.1 linkn.*1785_*1797delTGAAATTTCCAGT 3_prime_UTR_variant Exon 21 of 22 ENSP00000505343.1 A0A7P0T8W4
CUL4BENST00000680918.1 linkn.*1492_*1504delTGAAATTTCCAGT 3_prime_UTR_variant Exon 17 of 18 ENSP00000505955.1 A0A7P0Z4G9
CUL4BENST00000681080.1 linkn.*1785_*1797delTGAAATTTCCAGT 3_prime_UTR_variant Exon 19 of 20 ENSP00000505898.1 A0A7P0Z4E4
CUL4BENST00000681189.1 linkn.*742_*754delTGAAATTTCCAGT 3_prime_UTR_variant Exon 19 of 20 ENSP00000505973.1 A0A7P0TAF9
CUL4BENST00000681333.1 linkn.*3469_*3481delTGAAATTTCCAGT 3_prime_UTR_variant Exon 16 of 17 ENSP00000505739.1 A0A7P0T9R8
CUL4BENST00000681908.1 linkn.*748_*760delTGAAATTTCCAGT 3_prime_UTR_variant Exon 19 of 20 ENSP00000505777.1 A0A7P0T9P5

Frequencies

GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-119663960; API