13-113228037-A-G

Position:

• chr13-113228037-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001008895.4(CUL4A):​c.430A>G​(p.Arg144Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

CUL4A (HGNC:2554): (cullin 4A) CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]

CUL4A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL4A	NM_001008895.4	c.430A>G	p.Arg144Gly	missense_variant	4/20	ENST00000375440.9	NP_001008895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL4A	ENST00000375440.9	c.430A>G	p.Arg144Gly	missense_variant	4/20	1	NM_001008895.4	ENSP00000364589.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.430A>G (p.R144G) alteration is located in exon 4 (coding exon 4) of the CUL4A gene. This alteration results from a A to G substitution at nucleotide position 430, causing the arginine (R) at amino acid position 144 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	.;T;.;.;T;.
Eigen	Benign	0.00050
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	.;D;D;.;D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	.;.;.;.;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D;D;D;.;D;.
REVEL	Uncertain	0.53
Sift	Benign	0.13	T;T;T;.;T;.
Sift4G	Benign	0.36	T;T;T;T;T;D
Polyphen		0.13	.;.;.;.;B;.
Vest4		0.91
MutPred		0.55		.;.;.;.;Gain of catalytic residue at W139 (P = 0);Gain of catalytic residue at W139 (P = 0);
MVP		0.97
MPC		0.53
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.65
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113882351;