Variant 17-3869877-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032294.3(CAMKK1):c.1136G>T(p.Ser379Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CAMKK1
NM_032294.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKK1	NM_032294.3 linkuse as main transcript	c.1136G>T	p.Ser379Ile	missense_variant	13/16	ENST00000348335.7	NP_115670.1	Q8N5S9-1
CAMKK1	NM_172206.2 linkuse as main transcript	c.1217G>T	p.Ser406Ile	missense_variant	13/16		NP_757343.2	Q8N5S9J3KPJ3
CAMKK1	NM_172207.3 linkuse as main transcript	c.1250G>T	p.Ser417Ile	missense_variant	14/16		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.1136G>T	p.Ser379Ile	missense_variant	13/16	1	NM_032294.3	ENSP00000323118.3	Q8N5S9-1
CAMKK1	ENST00000381769.6 linkuse as main transcript	c.1217G>T	p.Ser406Ile	missense_variant	13/16	1		ENSP00000371188.2	J3KPJ3
CAMKK1	ENST00000158166.5 linkuse as main transcript	c.1250G>T	p.Ser417Ile	missense_variant	14/16	1		ENSP00000158166.5	Q8N5S9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251418

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000130

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727234

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:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 20, 2024

The c.1136G>T (p.S379I) alteration is located in exon 13 (coding exon 12) of the CAMKK1 gene. This alteration results from a G to T substitution at nucleotide position 1136, causing the serine (S) at amino acid position 379 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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.79

D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.7

.;M;.

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.96

.;D;.

Vest4

0.65

MVP

0.87

MPC

1.1

ClinPred

0.99

GERP RS

4.6

Varity_R

0.96

gMVP

0.88

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