X-120560500-T-G

Variant names:

• chrX-120560500-T-G
• rs145134351
• NM_001079872.2:c.139A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001079872.2(CUL4B):​c.139A>C​(p.Ser47Arg) 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 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)
• Consequence: CUL4B NM_001079872.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33502778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4B	NM_001079872.2	c.139A>C	p.Ser47Arg	missense_variant	Exon 1 of 20	ENST00000371322.11	NP_001073341.1
CUL4B	NM_003588.4	c.193A>C	p.Ser65Arg	missense_variant	Exon 3 of 22		NP_003579.3
CUL4B	NM_001330624.2	c.154A>C	p.Ser52Arg	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.139A>C	p.Ser47Arg	missense_variant	Exon 1 of 20	1	NM_001079872.2	ENSP00000360373.5
CUL4B	ENST00000681206.1	c.154A>C	p.Ser52Arg	missense_variant	Exon 2 of 23			ENSP00000505480.1
CUL4B	ENST00000680673.1	c.193A>C	p.Ser65Arg	missense_variant	Exon 3 of 22			ENSP00000505084.1
CUL4B	ENST00000681253.1	c.193A>C	p.Ser65Arg	missense_variant	Exon 4 of 23			ENSP00000506259.1
CUL4B	ENST00000681652.1	c.193A>C	p.Ser65Arg	missense_variant	Exon 6 of 25			ENSP00000505176.1
CUL4B	ENST00000336592.11	c.154A>C	p.Ser52Arg	missense_variant	Exon 2 of 21	5		ENSP00000338919.6
CUL4B	ENST00000674137.11	c.139A>C	p.Ser47Arg	missense_variant	Exon 1 of 20			ENSP00000501019.6
CUL4B	ENST00000681090.1	c.139A>C	p.Ser47Arg	missense_variant	Exon 1 of 20			ENSP00000506288.1
CUL4B	ENST00000404115.8	c.139A>C	p.Ser47Arg	missense_variant	Exon 1 of 19	1		ENSP00000384109.4
CUL4B	ENST00000679927.1	c.-207A>C		5_prime_UTR_variant	Exon 2 of 21			ENSP00000505603.1
CUL4B	ENST00000673919.1	n.139A>C		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000500994.1
CUL4B	ENST00000679432.1	n.124A>C		non_coding_transcript_exon_variant	Exon 1 of 22			ENSP00000505343.1
CUL4B	ENST00000681333.1	n.139A>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000505739.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	.;.;T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.0	.;.;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.35
MutPred		0.38		.;.;Loss of phosphorylation at S65 (P = 4e-04);
MVP		0.83
MPC		1.0
ClinPred		0.71	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.38

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: rs145134351; hg19: chrX-119694355;