22-46699412-G-C

Variant names:

• chr22-46699412-G-C
• rs144409797
• NM_022766.6:c.844C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022766.6(CERK):​c.844C>G​(p.Arg282Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R282H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CERK NM_022766.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 2 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERK	NM_022766.6	c.844C>G	p.Arg282Gly	missense_variant	Exon 8 of 13	ENST00000216264.13	NP_073603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERK	ENST00000216264.13	c.844C>G	p.Arg282Gly	missense_variant	Exon 8 of 13	1	NM_022766.6	ENSP00000216264.8
CERK	ENST00000443629.5	n.*222C>G		non_coding_transcript_exon_variant	Exon 7 of 12	1		ENSP00000400859.1
CERK	ENST00000443629.5	n.*222C>G		3_prime_UTR_variant	Exon 7 of 12	1		ENSP00000400859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		2.5
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.40
MutPred		0.63		Gain of sheet (P = 0.0101);
MVP		0.35
MPC		0.85
ClinPred		0.96	D
GERP RS		2.7
Varity_R		0.55
gMVP		0.83
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs144409797; hg19: chr22-47095309;