Variant 17-3873438-C-T 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.1021G>A(p.Val341Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CAMKK1
NM_032294.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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=0.10375473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3 linkuse as main transcript	c.1021G>A	p.Val341Ile	missense_variant	11/16	ENST00000348335.7	NP_115670.1	Q8N5S9-1
CAMKK1	NM_172206.2 linkuse as main transcript	c.1102G>A	p.Val368Ile	missense_variant	11/16		NP_757343.2	Q8N5S9J3KPJ3
CAMKK1	NM_172207.3 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	12/16		NP_757344.2	Q8N5S9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAMKK1	ENST00000348335.7 linkuse as main transcript	c.1021G>A	p.Val341Ile	missense_variant	11/16	1	NM_032294.3	ENSP00000323118.3	Q8N5S9-1
CAMKK1	ENST00000381769.6 linkuse as main transcript	c.1102G>A	p.Val368Ile	missense_variant	11/16	1		ENSP00000371188.2	J3KPJ3
CAMKK1	ENST00000158166.5 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	12/16	1		ENSP00000158166.5	Q8N5S9-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251432

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000719

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 16, 2024

The c.1021G>A (p.V341I) alteration is located in exon 11 (coding exon 10) of the CAMKK1 gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the valine (V) at amino acid position 341 to be replaced by an isoleucine (I). 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

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

DANN

Benign

0.96

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.054

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.17

.;B;.

Vest4

0.20

MVP

0.34

MPC

0.28

ClinPred

0.093

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.33

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

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