3-49859668-C-T

Variant names:

• chr3-49859668-C-T
• NM_024046.5:c.1156G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024046.5(CAMKV):​c.1156G>A​(p.Ala386Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.373
• Publications: 0 publications found

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061345786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKV	NM_024046.5	MANE Select	c.1156G>A	p.Ala386Thr	missense	Exon 11 of 11	NP_076951.2	Q8NCB2-1
	CAMKV	NM_001320147.2		c.1063G>A	p.Ala355Thr	missense	Exon 12 of 12	NP_001307076.1	Q8NCB2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKV	ENST00000477224.6	TSL:1 MANE Select	c.1156G>A	p.Ala386Thr	missense	Exon 11 of 11	ENSP00000419195.1	Q8NCB2-1
	CAMKV	ENST00000296471.11	TSL:1	c.1072G>A	p.Ala358Thr	missense	Exon 10 of 10	ENSP00000296471.6	Q8NCB2-2
	CAMKV	ENST00000620470.4	TSL:1	c.1072G>A	p.Ala358Thr	missense	Exon 9 of 9	ENSP00000484045.1	Q8NCB2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.37
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.028
Sift	Benign	0.065	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.043
MutPred		0.15		Gain of catalytic residue at A386 (P = 0.2416)
MVP		0.46
MPC		0.75
ClinPred		0.18	T
GERP RS		3.2
Varity_R		0.036
gMVP		0.087
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr3-49897101;