Variant 10-100190899-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278.5(CHUK):c.2178G>T(p.Glu726Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,459,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000011 ( 0 hom. )

Consequence

CHUK
NM_001278.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.115

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]

CHUK links:

CHUK (HGNC:):

CHUK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07265726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHUK	NM_001278.5 linkuse as main transcript	c.2178G>T	p.Glu726Asp	missense_variant	20/21	ENST00000370397.8	NP_001269.3	O15111
CHUK	XM_047424540.1 linkuse as main transcript	c.2178G>T	p.Glu726Asp	missense_variant	20/21		XP_047280496.1
CHUK	NM_001320928.2 linkuse as main transcript	c.*1G>T		3_prime_UTR_variant	20/21		NP_001307857.1
CHUK	XM_047424542.1 linkuse as main transcript	c.*1G>T		3_prime_UTR_variant	20/21		XP_047280498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHUK	ENST00000370397.8 linkuse as main transcript	c.2178G>T	p.Glu726Asp	missense_variant	20/21	1	NM_001278.5	ENSP00000359424.6	O15111
CHUK	ENST00000590930.5 linkuse as main transcript	n.3554G>T		non_coding_transcript_exon_variant	2/3	1
CHUK	ENST00000585551.1 linkuse as main transcript	n.196G>T		non_coding_transcript_exon_variant	2/2	3
CHUK	ENST00000588656.1 linkuse as main transcript	n.209G>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251478

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1459068

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726074

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:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.2178G>T (p.E726D) alteration is located in exon 20 (coding exon 20) of the CHUK gene. This alteration results from a G to T substitution at nucleotide position 2178, causing the glutamic acid (E) at amino acid position 726 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.0

DANN

Benign

0.65

DEOGEN2

Benign

0.060

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.79

M_CAP

Benign

0.0093

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.65

PrimateAI

Benign

0.46

PROVEAN

Benign

0.28

REVEL

Benign

0.094

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.046

Vest4

0.25

MutPred

0.18

Loss of disorder (P = 0.128);

MVP

0.33

MPC

0.56

ClinPred

0.11

GERP RS

0.84

Varity_R

0.067

gMVP

0.21

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over