Variant chr17-3883889-G-A 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.457C>T(p.His153Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

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: 4.06

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=0.09337422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAMKK1	NM_032294.3 linkuse as main transcript	c.457C>T	p.His153Tyr	missense_variant	4/16	ENST00000348335.7
CAMKK1	NM_172206.2 linkuse as main transcript	c.538C>T	p.His180Tyr	missense_variant	4/16
CAMKK1	NM_172207.3 linkuse as main transcript	c.457C>T	p.His153Tyr	missense_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMKK1	ENST00000348335.7 linkuse as main transcript	c.457C>T	p.His153Tyr	missense_variant	4/16	1	NM_032294.3	P1	Q8N5S9-1
CAMKK1	ENST00000381769.6 linkuse as main transcript	c.538C>T	p.His180Tyr	missense_variant	4/16	1
CAMKK1	ENST00000158166.5 linkuse as main transcript	c.457C>T	p.His153Tyr	missense_variant	4/16	1			Q8N5S9-2
CAMKK1	ENST00000573483.1 linkuse as main transcript	n.1165C>T		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251214

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135800

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461604

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727120

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000634

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 29, 2023

The c.457C>T (p.H153Y) alteration is located in exon 4 (coding exon 3) of the CAMKK1 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the histidine (H) at amino acid position 153 to be replaced by a tyrosine (Y). 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

0.090

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.060

.;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.27

.;N;N

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.081

Sift

Benign

0.99

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.30

MutPred

0.37

.;Gain of phosphorylation at H153 (P = 0.0103);Gain of phosphorylation at H153 (P = 0.0103);

MVP

0.73

MPC

0.37

ClinPred

0.21

GERP RS

4.0

Varity_R

0.12

gMVP

0.53

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