Variant 17-3862282-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032294.3(CAMKK1):c.1447A>C(p.Lys483Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,580,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CAMKK1
NM_032294.3 missense, splice_region

Scores

Splicing: ADA: 0.7508

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Variant links:

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]

CAMKK1 links:

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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=0.22629789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3 linkuse as main transcript	c.1447A>C	p.Lys483Gln	missense_variant, splice_region_variant	16/16	ENST00000348335.7	NP_115670.1	Q8N5S9-1
CAMKK1	NM_172206.2 linkuse as main transcript	c.1528A>C	p.Lys510Gln	missense_variant, splice_region_variant	16/16		NP_757343.2	Q8N5S9J3KPJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKK1	ENST00000348335.7 linkuse as main transcript	c.1447A>C	p.Lys483Gln	missense_variant, splice_region_variant	16/16	1	NM_032294.3	ENSP00000323118.3		Q8N5S9-1
CAMKK1	ENST00000381769.6 linkuse as main transcript	c.1528A>C	p.Lys510Gln	missense_variant, splice_region_variant	16/16	1		ENSP00000371188.2		J3KPJ3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1428122

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

707466

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:

0.00000366

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jul 14, 2024

The c.1447A>C (p.K483Q) alteration is located in exon 16 (coding exon 15) of the CAMKK1 gene. This alteration results from a A to C substitution at nucleotide position 1447, causing the lysine (K) at amino acid position 483 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

0.13

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.43

.;B

Vest4

0.26

MutPred

0.22

.;Loss of ubiquitination at K483 (P = 0.0071);

MVP

0.67

ClinPred

0.91

GERP RS

4.6

Varity_R

0.44

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.75

dbscSNV1_RF

Benign

0.66

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over