Variant 22-46690103-T-C 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_022766.6(CERK):c.1430A>G(p.Lys477Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,950 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

CERK
NM_022766.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

CERK (HGNC:19256): (ceramide kinase) CERK converts ceramide to ceramide 1-phosphate (C1P), a sphingolipid metabolite. Both CERK and C1P have been implicated in various cellular processes, including proliferation, apoptosis, phagocytosis, and inflammation (Kim et al., 2006 [PubMed 16488390]).[supplied by OMIM, Mar 2008]

CERK links:

CERK (HGNC:):

CERK 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=0.13519937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERK	NM_022766.6 linkuse as main transcript	c.1430A>G	p.Lys477Arg	missense_variant	12/13	ENST00000216264.13	NP_073603.2	Q8TCT0-1A0A024R4U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CERK	ENST00000216264.13 linkuse as main transcript	c.1430A>G	p.Lys477Arg	missense_variant	12/13	1	NM_022766.6	ENSP00000216264.8	Q8TCT0-1
CERK	ENST00000443629.5 linkuse as main transcript	n.*808A>G		non_coding_transcript_exon_variant	11/12	1		ENSP00000400859.1	F8WFD8
CERK	ENST00000443629.5 linkuse as main transcript	n.*808A>G		3_prime_UTR_variant	11/12	1		ENSP00000400859.1	F8WFD8
CERK	ENST00000471929.1 linkuse as main transcript	n.519A>G		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251404

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.1430A>G (p.K477R) alteration is located in exon 12 (coding exon 12) of the CERK gene. This alteration results from a A to G substitution at nucleotide position 1430, causing the lysine (K) at amino acid position 477 to be replaced by an arginine (R). 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

0.067

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Benign

0.0065

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Benign

0.10

Sift

Benign

0.18

Sift4G

Benign

0.28

Polyphen

0.0030

Vest4

0.25

MutPred

0.31

Loss of ubiquitination at K477 (P = 0.0081);

MVP

0.47

MPC

0.16

ClinPred

0.059

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.24

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