chr13-113210023-C-T

Variant names:

• chr13-113210023-C-T
• rs1166928710
• NM_001008895.4:c.199C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008895.4(CUL4A):​c.199C>T​(p.His67Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CUL4A NM_001008895.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24979687).

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.199C>T	p.His67Tyr	missense	Exon 2 of 20	NP_001008895.1	Q13619-1
	CUL4A	NM_001354943.2		c.199C>T	p.His67Tyr	missense	Exon 2 of 6	NP_001341872.1	A0A087WWN2
	CUL4A	NM_001278514.3		c.-102C>T		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.199C>T	p.His67Tyr	missense	Exon 2 of 20	ENSP00000364589.4	Q13619-1
	CUL4A	ENST00000326335.8	TSL:1	c.-102C>T		5_prime_UTR	Exon 2 of 20	ENSP00000322132.5	A0A0A0MR50
	CUL4A	ENST00000375441.7	TSL:1	c.-102C>T		5_prime_UTR	Exon 2 of 20	ENSP00000364590.3	Q13619-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1374222 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 678334

African (AFR) AF: 0.00 AC: 0 AN: 28034

American (AMR) AF: 0.00 AC: 0 AN: 33586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24242

East Asian (EAS) AF: 0.00 AC: 0 AN: 31982

South Asian (SAS) AF: 0.00 AC: 0 AN: 77170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069714

Other (OTH) AF: 0.00 AC: 0 AN: 56756

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.98
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.011	D
Polyphen		0.018	B
Vest4		0.36
MutPred		0.48		Loss of ubiquitination at K65 (P = 0.0787)
MVP		0.62
MPC		0.48
ClinPred		0.68	D
GERP RS		4.4
PromoterAI		0.19	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.30
Mutation Taster		=74/26	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: rs1166928710; hg19: chr13-113864337; COSMIC: COSV55812702; COSMIC: COSV55812702;