5-111224628-G-A

Position:

• chr5-111224628-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001744.6(CAMK4):​c.145G>A​(p.Glu49Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK4 NM_001744.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK4	NM_001744.6	c.145G>A	p.Glu49Lys	missense_variant	1/11	ENST00000282356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK4	ENST00000282356.9	c.145G>A	p.Glu49Lys	missense_variant	1/11	1	NM_001744.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	33
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0079	T;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.33	.;N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.95	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.96	.;D;D
Vest4		0.59, 0.38
MutPred		0.47		Gain of ubiquitination at E49 (P = 0.0388);Gain of ubiquitination at E49 (P = 0.0388);Gain of ubiquitination at E49 (P = 0.0388);
MVP		0.59
MPC		0.86
ClinPred		0.78	D
GERP RS		4.3
Varity_R		0.44
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.46		Position offset: -4

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

Publications

LitVar

Other links and lift over

dbSNP: rs765112045; hg19: chr5-110560326;