22-46691703-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022766.6(CERK):c.1201C>T(p.Arg401Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
CERK
NM_022766.6 missense
NM_022766.6 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 6.05
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 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=0.26359665).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERK | NM_022766.6 | c.1201C>T | p.Arg401Cys | missense_variant | 11/13 | ENST00000216264.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERK | ENST00000216264.13 | c.1201C>T | p.Arg401Cys | missense_variant | 11/13 | 1 | NM_022766.6 | P1 | |
CERK | ENST00000443629.5 | c.*579C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/12 | 1 | ||||
CERK | ENST00000471929.1 | n.290C>T | non_coding_transcript_exon_variant | 3/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251026Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135834
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461680Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727130
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74344
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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 | Jul 06, 2022 | The c.1201C>T (p.R401C) alteration is located in exon 11 (coding exon 11) of the CERK gene. This alteration results from a C to T substitution at nucleotide position 1201, causing the arginine (R) at amino acid position 401 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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