22-46699376-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_022766.6(CERK):c.880G>A(p.Gly294Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
CERK
NM_022766.6 missense
NM_022766.6 missense
Scores
13
3
3
Clinical Significance
Conservation
PhyloP100: 7.17
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.983
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERK | NM_022766.6 | c.880G>A | p.Gly294Arg | missense_variant | 8/13 | ENST00000216264.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERK | ENST00000216264.13 | c.880G>A | p.Gly294Arg | missense_variant | 8/13 | 1 | NM_022766.6 | P1 | |
CERK | ENST00000443629.5 | c.*258G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251482Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727226
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74320
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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 | Jan 04, 2022 | The c.880G>A (p.G294R) alteration is located in exon 8 (coding exon 8) of the CERK gene. This alteration results from a G to A substitution at nucleotide position 880, causing the glycine (G) at amino acid position 294 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0534);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at