X-120526817-G-A

Variant names:

• chrX-120526817-G-A
• rs1257568293
• NM_001079872.2:c.2632C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001079872.2(CUL4B):​c.2632C>T​(p.Arg878Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.2632C>T	p.Arg878Trp	missense_variant	Exon 20 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.2686C>T	p.Arg896Trp	missense_variant	Exon 22 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.2647C>T	p.Arg883Trp	missense_variant	Exon 21 of 21		NP_001317553.1
CUL4B	NM_001369145.1	c.2098C>T	p.Arg700Trp	missense_variant	Exon 20 of 20		NP_001356074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4B	ENST00000371322.11	c.2632C>T	p.Arg878Trp	missense_variant	Exon 20 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.2746C>T	p.Arg916Trp	missense_variant	Exon 23 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.2686C>T	p.Arg896Trp	missense_variant	Exon 22 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.2686C>T	p.Arg896Trp	missense_variant	Exon 23 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.2686C>T	p.Arg896Trp	missense_variant	Exon 25 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.2647C>T	p.Arg883Trp	missense_variant	Exon 21 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.2638C>T	p.Arg880Trp	missense_variant	Exon 20 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.2539C>T	p.Arg847Trp	missense_variant	Exon 20 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.2479C>T	p.Arg827Trp	missense_variant	Exon 19 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.2287C>T	p.Arg763Trp	missense_variant	Exon 21 of 21			ENSP00000505603.1
CUL4B	ENST00000371323.3	c.2098C>T	p.Arg700Trp	missense_variant	Exon 20 of 20	5		ENSP00000360374.3
CUL4B	ENST00000679844.1	c.1969C>T	p.Arg657Trp	missense_variant	Exon 18 of 18			ENSP00000505239.1
CUL4B	ENST00000680474	c.*78C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000505562.1
CUL4B	ENST00000673919.1	n.*2079C>T		non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.*188C>T		non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1841C>T		non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1841C>T		non_coding_transcript_exon_variant	Exon 22 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1548C>T		non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1841C>T		non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*798C>T		non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3525C>T		non_coding_transcript_exon_variant	Exon 17 of 17			ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*804C>T		non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000505777.1
CUL4B	ENST00000673919.1	n.*2079C>T		3_prime_UTR_variant	Exon 21 of 21			ENSP00000500994.1
CUL4B	ENST00000674073.2	n.*188C>T		3_prime_UTR_variant	Exon 18 of 18			ENSP00000501262.2
CUL4B	ENST00000679405.1	n.*1841C>T		3_prime_UTR_variant	Exon 22 of 22			ENSP00000504985.1
CUL4B	ENST00000679432.1	n.*1841C>T		3_prime_UTR_variant	Exon 22 of 22			ENSP00000505343.1
CUL4B	ENST00000680918.1	n.*1548C>T		3_prime_UTR_variant	Exon 18 of 18			ENSP00000505955.1
CUL4B	ENST00000681080.1	n.*1841C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000505898.1
CUL4B	ENST00000681189.1	n.*798C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000505973.1
CUL4B	ENST00000681333.1	n.*3525C>T		3_prime_UTR_variant	Exon 17 of 17			ENSP00000505739.1
CUL4B	ENST00000681908.1	n.*804C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000505777.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1082382 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 349764

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: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	.;.;D
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.1	.;.;H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.4	D;D;D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.74
MutPred		0.79		.;.;Loss of disorder (P = 0.0016);
MVP		0.96
MPC		3.0
ClinPred		1.0	D
GERP RS		1.2
Varity_R		0.93
gMVP		0.91

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

LitVar

Other links and lift over

dbSNP: rs1257568293; hg19: chrX-119660672;