chr5-111224521-C-G

Variant summary

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

The NM_001744.6(CAMK4):ā€‹c.38C>Gā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000057 ( 0 hom. )

Consequence

CAMK4
NM_001744.6 missense

Scores

6
13

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]

Genome browser will be placed here

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
CAMK4NM_001744.6 linkuse as main transcriptc.38C>G p.Ser13Cys missense_variant 1/11 ENST00000282356.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMK4ENST00000282356.9 linkuse as main transcriptc.38C>G p.Ser13Cys missense_variant 1/111 NM_001744.6 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000286
AC:
7
AN:
244478
Hom.:
0
AF XY:
0.0000526
AC XY:
7
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:
83
AN:
1459100
Hom.:
0
Cov.:
31
AF XY:
0.0000455
AC XY:
33
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.:
32
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 10, 2022The 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
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
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
D
LIST_S2
Benign
0.67
T;.;T
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Benign
0.69
.;N;N
MutationTaster
Benign
0.54
N;N
PrimateAI
Uncertain
0.72
T
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
T
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.

Other links and lift over

dbSNP: rs753581560; hg19: chr5-110560219; API