rs1455037982

Variant names:

• chr13-113210000-C-G
• rs1455037982
• NM_001008895.4:c.176C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-113210000-C-G
• chr13-113210000-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001008895.4(CUL4A):​c.176C>G​(p.Thr59Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 1,521,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.45
• 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, 0.795

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.176C>G	p.Thr59Arg	missense	Exon 2 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001354943.2		c.176C>G	p.Thr59Arg	missense	Exon 2 of 6	NP_001341872.1	A0A087WWN2
	CUL4A	NM_001278514.3		c.-125C>G		5_prime_UTR	Exon 2 of 20	NP_001265443.1	A0A0A0MR50

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL4A	ENST00000375440.9	TSL:1 MANE Select	c.176C>G	p.Thr59Arg	missense	Exon 2 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.-125C>G		5_prime_UTR	Exon 2 of 20	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.-125C>G		5_prime_UTR	Exon 2 of 20	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1369308 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675650

African (AFR) AF: 0.00 AC: 0 AN: 27796

American (AMR) AF: 0.00 AC: 0 AN: 32926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24136

East Asian (EAS) AF: 0.00 AC: 0 AN: 31532

South Asian (SAS) AF: 0.00 AC: 0 AN: 76882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4844

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1067398

Other (OTH) AF: 0.00 AC: 0 AN: 56510

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152062 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

ClinVar

ClinVar submissions

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	Benign	0.30
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.082
Eigen_PC	Benign	0.099
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.18	N
REVEL	Uncertain	0.42
Sift	Benign	0.094	T
Sift4G	Benign	0.38	T
Polyphen		0.57	P
Vest4		0.83
MutPred		0.46		Gain of MoRF binding (P = 0.043)
MVP		0.82
MPC		0.57
ClinPred		0.87	D
GERP RS		4.2
PromoterAI		0.0063	Neutral
Varity_R		0.54
gMVP		0.67
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1455037982; hg19: chr13-113864314;