rs1556214312

Variant names:

• chrX-120544607-TATA-T
• rs1556214312
• NM_001079872.2:c.954_956delTAT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001079872.2(CUL4B):​c.954_956delTAT​(p.Ile319del) variant causes a disruptive inframe deletion 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. I318I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CUL4B NM_001079872.2 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 9.25
• 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

LOC124905273 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001079872.2. Strenght limited to Supporting due to length of the change: 1aa.

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.954_956delTAT	p.Ile319del	disruptive_inframe_deletion	Exon 6 of 20	NP_001073341.1	Q13620-1
	CUL4B	NM_003588.4		c.1008_1010delTAT	p.Ile337del	disruptive_inframe_deletion	Exon 8 of 22	NP_003579.3
	CUL4B	NM_001330624.2		c.969_971delTAT	p.Ile324del	disruptive_inframe_deletion	Exon 7 of 21	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.954_956delTAT	p.Ile319del	disruptive_inframe_deletion	Exon 6 of 20	ENSP00000360373.5	Q13620-1
	CUL4B	ENST00000681206.1		c.1068_1070delTAT	p.Ile357del	disruptive_inframe_deletion	Exon 9 of 23	ENSP00000505480.1	A0A7P0T954
	CUL4B	ENST00000680673.1		c.1008_1010delTAT	p.Ile337del	disruptive_inframe_deletion	Exon 8 of 22	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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	X-linked intellectual disability Cabezas type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1556214312; hg19: chrX-119678462;