14-103522033-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001823.5(CKB):ā€‹c.338A>Gā€‹(p.Asp113Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,170 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 32)
Exomes š‘“: 7.2e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CKB
NM_001823.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.369
Variant links:
Genes affected
CKB (HGNC:1991): (creatine kinase B) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in brain as well as in other tissues, and as a heterodimer with a similar muscle isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. A pseudogene of this gene has been characterized. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.20434627).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CKBNM_001823.5 linkuse as main transcriptc.338A>G p.Asp113Gly missense_variant 3/8 ENST00000348956.7
CKBNM_001362531.2 linkuse as main transcriptc.338A>G p.Asp113Gly missense_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CKBENST00000348956.7 linkuse as main transcriptc.338A>G p.Asp113Gly missense_variant 3/81 NM_001823.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
147200
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000649
AC:
1
AN:
154084
Hom.:
0
AF XY:
0.0000122
AC XY:
1
AN XY:
82202
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000228
GnomAD4 exome
AF:
7.20e-7
AC:
1
AN:
1388170
Hom.:
0
Cov.:
40
AF XY:
0.00000146
AC XY:
1
AN XY:
685040
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
147200
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
71780
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 08, 2023The c.338A>G (p.D113G) alteration is located in exon 3 (coding exon 2) of the CKB gene. This alteration results from a A to G substitution at nucleotide position 338, causing the aspartic acid (D) at amino acid position 113 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.75
D;T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.078
D
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.069
Sift
Uncertain
0.026
D;D;D
Sift4G
Benign
0.34
T;.;.
Polyphen
0.0
B;.;.
Vest4
0.11
MutPred
0.33
Gain of catalytic residue at N114 (P = 0);Gain of catalytic residue at N114 (P = 0);.;
MVP
0.33
MPC
1.2
ClinPred
0.32
T
GERP RS
4.2
Varity_R
0.42
gMVP
0.69

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: rs1370684683; hg19: chr14-103988370; API