10-100205167-G-C

Variant names:

• chr10-100205167-G-C
• NM_001278.5:c.1264C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHUK NM_001278.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.27

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]

ACMG classification

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
CHUK	NM_001278.5	c.1264C>G	p.Gln422Glu	missense_variant	Exon 12 of 21	ENST00000370397.8	NP_001269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHUK	ENST00000370397.8	c.1264C>G	p.Gln422Glu	missense_variant	Exon 12 of 21	1	NM_001278.5	ENSP00000359424.6

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

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;