10-100205167-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001278.5(CHUK):​c.1264C>G​(p.Gln422Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CHUK
NM_001278.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.27
Variant links:
Genes affected
CHUK (HGNC:1974): (component of inhibitor of nuclear factor kappa B kinase complex) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26734328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHUKNM_001278.5 linkc.1264C>G p.Gln422Glu missense_variant Exon 12 of 21 ENST00000370397.8 NP_001269.3 O15111

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHUKENST00000370397.8 linkc.1264C>G p.Gln422Glu missense_variant Exon 12 of 21 1 NM_001278.5 ENSP00000359424.6 O15111

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461634
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727130
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.13
T
Eigen
Benign
0.047
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.27
N
REVEL
Benign
0.14
Sift
Benign
0.30
T
Sift4G
Benign
0.84
T
Polyphen
0.67
P
Vest4
0.23
MutPred
0.49
Loss of MoRF binding (P = 0.0774);
MVP
0.83
MPC
0.61
ClinPred
0.46
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-101964924; API