NM_001079872.2:c.139_141delAGCinsCGA

Variant names:

• chrX-120560498-GCT-TCG
• NM_001079872.2:c.139_141delAGCinsCGA
• CUL4B p.Ser47Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001079872.2(CUL4B):​c.139_141delAGCinsCGA​(p.Ser47Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S47G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 0 publications found

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]

CUL4B Gene-Disease associations (from GenCC):

• X-linked intellectual disability, Cabezas type

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079872.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	NM_001079872.2	MANE Select	c.139_141delAGCinsCGA	p.Ser47Arg	missense	N/A	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.193_195delAGCinsCGA	p.Ser65Arg	missense	N/A	NP_003579.3
	CUL4B	NM_001330624.2		c.154_156delAGCinsCGA	p.Ser52Arg	missense	N/A	NP_001317553.1	K4DI93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4B	ENST00000371322.11	TSL:1 MANE Select	c.139_141delAGCinsCGA	p.Ser47Arg	missense	N/A	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.154_156delAGCinsCGA	p.Ser52Arg	missense	N/A	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.193_195delAGCinsCGA	p.Ser65Arg	missense	N/A	ENSP00000505084.1	Q13620-2

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-119694353;