rs777179632

Variant names:

• chr3-49861276-G-A
• rs777179632
• NM_024046.5:c.466C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024046.5(CAMKV):​c.466C>T​(p.Arg156Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41

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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.466C>T	p.Arg156Trp	missense_variant	Exon 6 of 11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.466C>T	p.Arg156Trp	missense_variant	Exon 6 of 12		NP_001307076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6	c.466C>T	p.Arg156Trp	missense_variant	Exon 6 of 11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251452 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461838 Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466C>T (p.R156W) alteration is located in exon 6 (coding exon 5) of the CAMKV gene. This alteration results from a C to T substitution at nucleotide position 466, causing the arginine (R) at amino acid position 156 to be replaced by a tryptophan (W). 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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;.;T;T;.;T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	.;D;D;D;D;D;D;D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.6	M;M;.;M;M;.;.;.
PhyloP100		3.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.4	D;D;D;D;.;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.064	T;T;T;T;.;D;T;D
Sift4G	Uncertain	0.024	D;D;D;D;D;.;D;D
Polyphen		1.0	D;D;.;D;D;.;D;.
Vest4		0.50
MutPred		0.45		Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);Loss of MoRF binding (P = 0.1017);.;.;.;
MVP		0.62
MPC		2.7
ClinPred		0.95	D
GERP RS		2.5
Varity_R		0.094
gMVP		0.81
Mutation Taster		=26/74	disease causing

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

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Other links and lift over

dbSNP: rs777179632; hg19: chr3-49898709; COSMIC: COSV56555844; COSMIC: COSV56555844;