NM_022766.6:c.1150G>A

Variant names:

• chr22-46691754-C-T
• rs143397270
• NM_022766.6:c.1150G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_022766.6(CERK):​c.1150G>A​(p.Val384Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,611,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V384F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00094 (1 hom.)
• Consequence: CERK NM_022766.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.285
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019758672).
• BP6: Variant 22-46691754-C-T is Benign according to our data. Variant chr22-46691754-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2332239.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1150G>A	p.Val384Ile	missense	Exon 11 of 13	NP_073603.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERK	ENST00000216264.13	TSL:1 MANE Select	c.1150G>A	p.Val384Ile	missense	Exon 11 of 13	ENSP00000216264.8	Q8TCT0-1
	CERK	ENST00000443629.5	TSL:1	n.*528G>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000400859.1	F8WFD8
	CERK	ENST00000443629.5	TSL:1	n.*528G>A		3_prime_UTR	Exon 10 of 12	ENSP00000400859.1	F8WFD8

Frequencies

GnomAD3 genomes AF: 0.000650 AC: 99 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.000955

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000659 AC: 165 AN: 250236 AF XY: 0.000716

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000937 AC: 1368 AN: 1459458 Hom.: 1 Cov.: 32 AF XY: 0.000943 AC XY: 684 AN XY: 725574

African (AFR) AF: 0.000209 AC: 7 AN: 33456

American (AMR) AF: 0.000515 AC: 23 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39636

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86190

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53310

Middle Eastern (MID) AF: 0.000883 AC: 5 AN: 5660

European-Non Finnish (NFE) AF: 0.00114 AC: 1264 AN: 1110146

Other (OTH) AF: 0.000796 AC: 48 AN: 60276

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.000658 AC XY: 49 AN XY: 74506

African (AFR) AF: 0.000361 AC: 15 AN: 41580

American (AMR) AF: 0.00111 AC: 17 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000955 AC: 65 AN: 68042

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000929

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000552 AC: 67

EpiCase AF: 0.00120

EpiControl AF: 0.00166

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.30
DANN	Benign	0.88
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.075	N
PhyloP100		0.28
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.016
Sift	Benign	0.58	T
Sift4G	Benign	0.73	T
Polyphen		0.0070	B
Vest4		0.16
MVP		0.12
MPC		0.16
ClinPred		0.0032	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.010
gMVP		0.18
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143397270; hg19: chr22-47087651; COSMIC: COSV99348657;