rs9306515

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_022766.6(CERK):​c.632C>T​(p.Thr211Met) variant causes a missense change. The variant allele was found at a frequency of 0.00244 in 1,613,812 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 40 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 42 hom. )

Consequence

CERK
NM_022766.6 missense

Scores

8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0053140223).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2074/152210) while in subpopulation AFR AF= 0.0477 (1982/41516). AF 95% confidence interval is 0.046. There are 40 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CERKNM_022766.6 linkuse as main transcriptc.632C>T p.Thr211Met missense_variant 6/13 ENST00000216264.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CERKENST00000216264.13 linkuse as main transcriptc.632C>T p.Thr211Met missense_variant 6/131 NM_022766.6 P1Q8TCT0-1
CERKENST00000443629.5 linkuse as main transcriptc.*10C>T 3_prime_UTR_variant, NMD_transcript_variant 5/121

Frequencies

GnomAD3 genomes
AF:
0.0136
AC:
2068
AN:
152092
Hom.:
39
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0477
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00406
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00907
GnomAD3 exomes
AF:
0.00326
AC:
819
AN:
250970
Hom.:
14
AF XY:
0.00226
AC XY:
307
AN XY:
135696
show subpopulations
Gnomad AFR exome
AF:
0.0452
Gnomad AMR exome
AF:
0.00168
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00128
AC:
1869
AN:
1461602
Hom.:
42
Cov.:
31
AF XY:
0.00111
AC XY:
810
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.0455
Gnomad4 AMR exome
AF:
0.00215
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.00272
GnomAD4 genome
AF:
0.0136
AC:
2074
AN:
152210
Hom.:
40
Cov.:
33
AF XY:
0.0139
AC XY:
1035
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0477
Gnomad4 AMR
AF:
0.00405
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00898
Alfa
AF:
0.00240
Hom.:
24
Bravo
AF:
0.0147
ESP6500AA
AF:
0.0463
AC:
204
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00412
AC:
500
Asia WGS
AF:
0.00202
AC:
8
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.89
D
MetaRNN
Benign
0.0053
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.1
D
REVEL
Benign
0.086
Sift
Benign
0.075
T
Sift4G
Benign
0.12
T
Polyphen
0.88
P
Vest4
0.21
MVP
0.32
MPC
0.52
ClinPred
0.028
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.067
gMVP
0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9306515; hg19: chr22-47103823; API