Variant 5-111224521-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_001744.6(CAMK4):c.38C>G(p.Ser13Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000569 in 1,459,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

CAMK4
NM_001744.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

CAMK4 (HGNC:1464): (calcium/calmodulin dependent protein kinase IV) The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

CAMK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1

In a modified_residue Phosphoserine; by autocatalysis (size 0) in uniprot entity KCC4_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.22472626).

BS2

High AC in GnomAdExome4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK4	NM_001744.6 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	1/11	ENST00000282356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK4	ENST00000282356.9 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	1/11	1	NM_001744.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000286

AC:

AN:

244478

Hom.:

AF XY:

0.0000526

AC XY:

AN XY:

133140

show subpopulations

Gnomad AFR exome

AF:

0.0000646

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:

0.0000548

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1459100

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725802

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:

0.0000729

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

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

Feb 10, 2022

The c.38C>G (p.S13C) alteration is located in exon 1 (coding exon 1) of the CAMK4 gene. This alteration results from a C to G substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a cysteine (C). 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

0.098

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.67

T;.;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.69

.;N;N

MutationTaster

Benign

0.54

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.013

D;T;T

Sift4G

Uncertain

0.050

T;T;T

Polyphen

0.97

.;D;D

Vest4

0.41, 0.34

MutPred

0.33

Loss of glycosylation at S13 (P = 0.0223);Loss of glycosylation at S13 (P = 0.0223);Loss of glycosylation at S13 (P = 0.0223);

MVP

0.82

MPC

1.6

ClinPred

0.20

GERP RS

3.8

Varity_R

0.15

gMVP

0.28

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