3-49859668-C-T

Position:

• chr3-49859668-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 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

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]

CAMKV (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.1156G>A	p.Ala386Thr	missense_variant	11/11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.1063G>A	p.Ala355Thr	missense_variant	12/12		NP_001307076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6	c.1156G>A	p.Ala386Thr	missense_variant	11/11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jul 13, 2021

The c.1156G>A (p.A386T) alteration is located in exon 11 (coding exon 10) of the CAMKV gene. This alteration results from a G to A substitution at nucleotide position 1156, causing the alanine (A) at amino acid position 386 to be replaced by a threonine (T). 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	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.062	.;.;T;.;T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.67	.;T;T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.061	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.46	N;N;N;.;N;N
REVEL	Benign	0.028
Sift	Benign	0.065	T;T;T;.;T;T
Sift4G	Benign	0.46	T;T;T;T;.;T
Polyphen		0.0010	B;B;B;B;B;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

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: chr3-49897101;