chr13-113209730-G-T

Variant names:

• chr13-113209730-G-T
• rs1163049031
• NM_001008895.4:c.103G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001008895.4(CUL4A):​c.103G>T​(p.Gly35Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,016,484 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G35R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.103G>T	p.Gly35Trp	missense	Exon 1 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001354943.2		c.103G>T	p.Gly35Trp	missense	Exon 1 of 6	NP_001341872.1	A0A087WWN2
	CUL4A	NM_001354940.2		c.-173G>T		5_prime_UTR	Exon 1 of 20	NP_001341869.1	Q13619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4A	ENST00000375440.9	TSL:1 MANE Select	c.103G>T	p.Gly35Trp	missense	Exon 1 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.-152-243G>T		intron	N/A	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.-152-243G>T		intron	N/A	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000197 AC: 2 AN: 1016484 Hom.: 0 Cov.: 30 AF XY: 0.00000209 AC XY: 1 AN XY: 479360

African (AFR) AF: 0.00 AC: 0 AN: 20668

American (AMR) AF: 0.00 AC: 0 AN: 6272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11280

East Asian (EAS) AF: 0.00 AC: 0 AN: 21118

South Asian (SAS) AF: 0.00 AC: 0 AN: 19124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2588

European-Non Finnish (NFE) AF: 0.00000228 AC: 2 AN: 878850

Other (OTH) AF: 0.00 AC: 0 AN: 38718

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.080
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.39
MutPred		0.41		Gain of catalytic residue at A37 (P = 0)
MVP		0.85
MPC		0.72
ClinPred		0.81	D
GERP RS		3.6
PromoterAI		0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.085
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1163049031; hg19: chr13-113864044;