chr13-113228037-A-G

Variant names:

• chr13-113228037-A-G
• NM_001008895.4:c.430A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008895.4. 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
	CUL4A	NM_001008895.4	MANE Select	c.430A>G	p.Arg144Gly	missense	Exon 4 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001278514.3		c.130A>G	p.Arg44Gly	missense	Exon 4 of 20	NP_001265443.1	A0A0A0MR50
	CUL4A	NM_001278513.3		c.130A>G	p.Arg44Gly	missense	Exon 4 of 20	NP_001265442.1	Q13619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4A	ENST00000375440.9	TSL:1 MANE Select	c.430A>G	p.Arg144Gly	missense	Exon 4 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.130A>G	p.Arg44Gly	missense	Exon 4 of 20	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.130A>G	p.Arg44Gly	missense	Exon 4 of 20	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.00050
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.53
Sift	Benign	0.13	T
Sift4G	Benign	0.36	T
Polyphen		0.13	B
Vest4		0.91
MutPred		0.55		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
Mutation Taster		=40/60	disease causing

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

hg19: chr13-113882351;