X-120560345-C-G

Variant names:

• chrX-120560345-C-G
• NM_001079872.2:c.294G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001079872.2(CUL4B):​c.294G>C​(p.Gln98His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21498871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.294G>C	p.Gln98His	missense_variant	Exon 1 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.348G>C	p.Gln116His	missense_variant	Exon 3 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.309G>C	p.Gln103His	missense_variant	Exon 2 of 21		NP_001317553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.294G>C	p.Gln98His	missense_variant	Exon 1 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.309G>C	p.Gln103His	missense_variant	Exon 2 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.348G>C	p.Gln116His	missense_variant	Exon 3 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.348G>C	p.Gln116His	missense_variant	Exon 4 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.348G>C	p.Gln116His	missense_variant	Exon 6 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.309G>C	p.Gln103His	missense_variant	Exon 2 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.294G>C	p.Gln98His	missense_variant	Exon 1 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.294G>C	p.Gln98His	missense_variant	Exon 1 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.294G>C	p.Gln98His	missense_variant	Exon 1 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.-52G>C		5_prime_UTR_variant	Exon 2 of 21			ENSP00000505603.1
CUL4B	ENST00000673919.1	n.294G>C		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000500994.1
CUL4B	ENST00000679432.1	n.279G>C		non_coding_transcript_exon_variant	Exon 1 of 22			ENSP00000505343.1
CUL4B	ENST00000681333.1	n.294G>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000505739.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096055 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 1 AN XY: 361637

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	.;.;T
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.85	D;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.81	.;.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.077	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.28
MutPred		0.20		.;.;Gain of relative solvent accessibility (P = 0.0522);
MVP		0.93
MPC		0.60
ClinPred		0.63	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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-119694200;