rs147136485

Variant names:

• chr13-113233203-C-G
• rs147136485
• NM_001008895.4:c.539C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-113233203-C-G
• chr13-113233203-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008895.4(CUL4A):​c.539C>G​(p.Thr180Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12460297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL4A	NM_001008895.4	c.539C>G	p.Thr180Ser	missense_variant	Exon 6 of 20	ENST00000375440.9	NP_001008895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL4A	ENST00000375440.9	c.539C>G	p.Thr180Ser	missense_variant	Exon 6 of 20	1	NM_001008895.4	ENSP00000364589.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.2
DANN	Benign	0.31
DEOGEN2	Benign	0.0055	.;T;.;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.46	.;T;T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.18	.;.;.;.;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.42	N;.;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.69	T;.;T;.;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.0	.;.;.;.;B
Vest4		0.30
MutPred		0.42		.;.;.;.;Gain of catalytic residue at R179 (P = 0);
MVP		0.36
MPC		0.36
ClinPred		0.042	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.048

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: rs147136485; hg19: chr13-113887517;