17-3883889-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032294.3(CAMKK1):c.457C>T(p.His153Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CAMKK1
NM_032294.3 missense
NM_032294.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.06
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09337422).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAMKK1 | NM_032294.3 | c.457C>T | p.His153Tyr | missense_variant | 4/16 | ENST00000348335.7 | |
CAMKK1 | NM_172206.2 | c.538C>T | p.His180Tyr | missense_variant | 4/16 | ||
CAMKK1 | NM_172207.3 | c.457C>T | p.His153Tyr | missense_variant | 4/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMKK1 | ENST00000348335.7 | c.457C>T | p.His153Tyr | missense_variant | 4/16 | 1 | NM_032294.3 | P1 | |
CAMKK1 | ENST00000381769.6 | c.538C>T | p.His180Tyr | missense_variant | 4/16 | 1 | |||
CAMKK1 | ENST00000158166.5 | c.457C>T | p.His153Tyr | missense_variant | 4/16 | 1 | |||
CAMKK1 | ENST00000573483.1 | n.1165C>T | non_coding_transcript_exon_variant | 4/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251214Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135800
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461604Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727120
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GnomAD4 genome Cov.: 32
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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 | Sep 29, 2023 | The c.457C>T (p.H153Y) alteration is located in exon 4 (coding exon 3) of the CAMKK1 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the histidine (H) at amino acid position 153 to be replaced by a tyrosine (Y). 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
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.0010
.;B;.
Vest4
MutPred
0.37
.;Gain of phosphorylation at H153 (P = 0.0103);Gain of phosphorylation at H153 (P = 0.0103);
MVP
MPC
0.37
ClinPred
T
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