17-3869830-C-G

Position:

• chr17-3869830-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032294.3(CAMKK1):​c.1183G>C​(p.Glu395Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: CAMKK1 NM_032294.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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]

ACMG classification

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=0.2555422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3	c.1183G>C	p.Glu395Gln	missense_variant	13/16	ENST00000348335.7	NP_115670.1
CAMKK1	NM_172206.2	c.1264G>C	p.Glu422Gln	missense_variant	13/16		NP_757343.2
CAMKK1	NM_172207.3	c.1297G>C	p.Glu433Gln	missense_variant	14/16		NP_757344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK1	ENST00000348335.7	c.1183G>C	p.Glu395Gln	missense_variant	13/16	1	NM_032294.3	ENSP00000323118.3
CAMKK1	ENST00000381769.6	c.1264G>C	p.Glu422Gln	missense_variant	13/16	1		ENSP00000371188.2
CAMKK1	ENST00000158166.5	c.1297G>C	p.Glu433Gln	missense_variant	14/16	1		ENSP00000158166.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.1183G>C (p.E395Q) alteration is located in exon 13 (coding exon 12) of the CAMKK1 gene. This alteration results from a G to C substitution at nucleotide position 1183, causing the glutamic acid (E) at amino acid position 395 to be replaced by a glutamine (Q). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.099	.;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0060	.;B;.
Vest4		0.18
MutPred		0.33		.;.;Loss of ubiquitination at K430 (P = 0.0524);
MVP		0.76
MPC		0.39
ClinPred		0.73	D
GERP RS		4.6
Varity_R		0.47
gMVP		0.31

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: chr17-3773124;