17-3880384-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032294.3(CAMKK1):c.758G>A(p.Arg253His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,708 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 1 hom. )
Consequence
CAMKK1
NM_032294.3 missense
NM_032294.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 7.38
Genes affected
CAMKK1 (HGNC:1469): (calcium/calmodulin dependent protein kinase kinase 1) The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade. Three transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAMKK1 | NM_032294.3 | c.758G>A | p.Arg253His | missense_variant | 9/16 | ENST00000348335.7 | NP_115670.1 | |
CAMKK1 | NM_172206.2 | c.839G>A | p.Arg280His | missense_variant | 9/16 | NP_757343.2 | ||
CAMKK1 | NM_172207.3 | c.872G>A | p.Arg291His | missense_variant | 10/16 | NP_757344.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAMKK1 | ENST00000348335.7 | c.758G>A | p.Arg253His | missense_variant | 9/16 | 1 | NM_032294.3 | ENSP00000323118.3 | ||
CAMKK1 | ENST00000381769.6 | c.839G>A | p.Arg280His | missense_variant | 9/16 | 1 | ENSP00000371188.2 | |||
CAMKK1 | ENST00000158166.5 | c.872G>A | p.Arg291His | missense_variant | 10/16 | 1 | ENSP00000158166.5 | |||
CAMKK1 | ENST00000573483.1 | n.2345G>A | non_coding_transcript_exon_variant | 8/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250568Hom.: 1 AF XY: 0.0000295 AC XY: 4AN XY: 135608
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461708Hom.: 1 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727110
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GnomAD4 genome Cov.: 33
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33
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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 | Apr 12, 2024 | The c.758G>A (p.R253H) alteration is located in exon 9 (coding exon 8) of the CAMKK1 gene. This alteration results from a G to A substitution at nucleotide position 758, causing the arginine (R) at amino acid position 253 to be replaced by a histidine (H). 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
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
0.15
.;B;.
Vest4
MutPred
0.73
.;.;Loss of catalytic residue at R291 (P = 0.097);
MVP
MPC
0.63
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