13-113210080-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001008895.4(CUL4A):​c.256C>T​(p.Leu86Phe) 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. 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. L86V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CUL4A
NM_001008895.4 missense

Scores

9
9
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUL4ANM_001008895.4 linkc.256C>T p.Leu86Phe missense_variant Exon 2 of 20 ENST00000375440.9 NP_001008895.1 Q13619-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUL4AENST00000375440.9 linkc.256C>T p.Leu86Phe missense_variant Exon 2 of 20 1 NM_001008895.4 ENSP00000364589.4 Q13619-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1352494
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
667138
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Uncertain
0.52
D
MutationAssessor
Pathogenic
3.8
H;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Pathogenic
0.76
Sift
Uncertain
0.0010
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.85
MutPred
0.70
Gain of catalytic residue at Q88 (P = 0.0011);Gain of catalytic residue at Q88 (P = 0.0011);
MVP
0.89
MPC
1.3
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.96
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761690889; hg19: chr13-113864394; API