3-49860489-T-C

Variant names:

• chr3-49860489-T-C
• NM_024046.5:c.836A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024046.5(CAMKV):​c.836A>G​(p.Glu279Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E279D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

Genes affected

CAMKV (HGNC:28788): (CaM kinase like vesicle associated) Predicted to enable calmodulin binding activity and calmodulin-dependent protein kinase activity. Predicted to be involved in peptidyl-serine phosphorylation. Predicted to be located in cytoplasmic vesicle membrane and plasma membrane. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.836A>G	p.Glu279Gly	missense_variant	Exon 9 of 11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.836A>G	p.Glu279Gly	missense_variant	Exon 9 of 12		NP_001307076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6	c.836A>G	p.Glu279Gly	missense_variant	Exon 9 of 11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.836A>G (p.E279G) alteration is located in exon 9 (coding exon 8) of the CAMKV gene. This alteration results from a A to G substitution at nucleotide position 836, causing the glutamic acid (E) at amino acid position 279 to be replaced by a glycine (G). 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	0.42
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;.;T;T;.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D;D;D;D;D;T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.0	.;M;.;M;.;.;.
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.3	D;D;D;D;.;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;D;D;D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;.;D
Polyphen		0.99	D;D;.;D;D;D;D
Vest4		0.69
MutPred		0.53		.;Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);.;.;.;
MVP		0.63
MPC		2.8
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.44
gMVP		0.94
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

hg19: chr3-49897922;