dbSNP rs779486682: CERK:p.Arg454Cys (chr22-46690173-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_022766.6(CERK):c.1360C>T(p.Arg454Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,461,806 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R454H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

CERK
NM_022766.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.909

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022766.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERK	NM_022766.6	MANE Select	c.1360C>T	p.Arg454Cys	missense	Exon 12 of 13	NP_073603.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERK	ENST00000216264.13	TSL:1 MANE Select	c.1360C>T	p.Arg454Cys	missense	Exon 12 of 13	ENSP00000216264.8	Q8TCT0-1
CERK	ENST00000443629.5	TSL:1	n.*738C>T		non_coding_transcript_exon	Exon 11 of 12	ENSP00000400859.1	F8WFD8
CERK	ENST00000443629.5	TSL:1	n.*738C>T		3_prime_UTR	Exon 11 of 12	ENSP00000400859.1	F8WFD8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251424

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000104

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.3

PhyloP100

4.1

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.94

MVP

0.36

MPC

0.91

ClinPred

0.99

GERP RS

4.9

Varity_R

0.68

gMVP

0.78

Mutation Taster

=20/80

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over