Genetic Variant CAMKK1:p.Pro46Leu (chr17-3885551-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032294.3(CAMKK1):c.137C>T(p.Pro46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P46R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CAMKK1
NM_032294.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10299432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKK1	NM_032294.3 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 16	ENST00000348335.7	NP_115670.1	Q8N5S9-1
CAMKK1	NM_172206.2 link	c.218C>T	p.Pro73Leu	missense_variant	Exon 2 of 16		NP_757343.2	Q8N5S9J3KPJ3
CAMKK1	NM_172207.3 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 16		NP_757344.2	Q8N5S9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAMKK1	ENST00000348335.7 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 16	1	NM_032294.3	ENSP00000323118.3	Q8N5S9-1
CAMKK1	ENST00000381769.6 link	c.218C>T	p.Pro73Leu	missense_variant	Exon 2 of 16	1		ENSP00000371188.2	J3KPJ3
CAMKK1	ENST00000158166.5 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 16	1		ENSP00000158166.5	Q8N5S9-2
CAMKK1	ENST00000573483.1 link	n.845C>T		non_coding_transcript_exon_variant	Exon 2 of 8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.082

.;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N;N

PhyloP100

0.43

PrimateAI

Benign

0.41

PROVEAN

Benign

0.47

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.16

MutPred

0.23

.;Loss of glycosylation at P46 (P = 0.0343);Loss of glycosylation at P46 (P = 0.0343);

MVP

0.80

MPC

0.33

ClinPred

0.12

GERP RS

3.9

Varity_R

0.040

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over