2-44362111-C-G

Variant summary

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

The NM_024766.5(CAMKMT):ā€‹c.104C>Gā€‹(p.Pro35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.6e-7 ( 0 hom. )

Consequence

CAMKMT
NM_024766.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
CAMKMT (HGNC:26276): (calmodulin-lysine N-methyltransferase) This gene encodes a class I protein methyltransferase that acts in the formation of trimethyllysine in calmodulin. The protein contains a AdoMet-binding motif and may play a role in calcium-dependent signaling. [provided by RefSeq, Sep 2012]

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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=0.19853151).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAMKMTNM_024766.5 linkuse as main transcriptc.104C>G p.Pro35Arg missense_variant 1/11 ENST00000378494.8 NP_079042.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAMKMTENST00000378494.8 linkuse as main transcriptc.104C>G p.Pro35Arg missense_variant 1/111 NM_024766.5 ENSP00000367755 P1Q7Z624-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.59e-7
AC:
1
AN:
1317672
Hom.:
0
Cov.:
31
AF XY:
0.00000154
AC XY:
1
AN XY:
650188
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:
0.0000145
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 16, 2023The c.104C>G (p.P35R) alteration is located in exon 1 (coding exon 1) of the CAMKMT gene. This alteration results from a C to G substitution at nucleotide position 104, causing the proline (P) at amino acid position 35 to be replaced by an arginine (R). 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
0.092
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
.;T;.;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;.;L;L
MutationTaster
Benign
0.98
N;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.4
N;N;N;N
REVEL
Benign
0.077
Sift
Uncertain
0.0090
D;D;D;T
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.83, 0.23
.;.;P;B
Vest4
0.31
MutPred
0.53
Gain of MoRF binding (P = 0.0028);Gain of MoRF binding (P = 0.0028);Gain of MoRF binding (P = 0.0028);Gain of MoRF binding (P = 0.0028);
MVP
0.54
MPC
0.082
ClinPred
0.52
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.078
gMVP
0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44589250; API