5-111473335-C-T

Position:

• chr5-111473335-C-T

Variant summary

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

The NM_001744.6(CAMK4):​c.650C>T​(p.Ala217Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMK4 NM_001744.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30

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	Protein	UniProt
CAMK4	NM_001744.6	c.650C>T	p.Ala217Val	missense_variant	8/11	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.650C>T	p.Ala217Val	missense_variant	8/11	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.650C>T (p.A217V) alteration is located in exon 8 (coding exon 8) of the CAMK4 gene. This alteration results from a C to T substitution at nucleotide position 650, causing the alanine (A) at amino acid position 217 to be replaced by a valine (V). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	D;D
Vest4		0.51
MutPred		0.51		Loss of catalytic residue at A217 (P = 0.1345);Loss of catalytic residue at A217 (P = 0.1345);
MVP		0.90
MPC		1.7
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.41
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-110809033;