3-49860994-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024046.5(CAMKV):​c.587G>A​(p.Arg196Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,864 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: 0.0000062 ( 0 hom. )

Consequence

CAMKV
NM_024046.5 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAMKVNM_024046.5 linkc.587G>A p.Arg196Gln missense_variant 7/11 ENST00000477224.6 NP_076951.2 Q8NCB2-1A0A140VKD5
CAMKVNM_001320147.2 linkc.587G>A p.Arg196Gln missense_variant 7/12 NP_001307076.1 Q8NCB2-3A0A024R331

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAMKVENST00000477224.6 linkc.587G>A p.Arg196Gln missense_variant 7/111 NM_024046.5 ENSP00000419195.1 Q8NCB2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251372
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461864
Hom.:
0
Cov.:
36
AF XY:
0.00000550
AC XY:
4
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 20, 2023The c.587G>A (p.R196Q) alteration is located in exon 7 (coding exon 6) of the CAMKV gene. This alteration results from a G to A substitution at nucleotide position 587, causing the arginine (R) at amino acid position 196 to be replaced by a glutamine (Q). 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
0.52
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.0052
.;T;T;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D;D;D
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.54
D;D;D;D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
0.40
N;.;N;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.64
N;N;N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.020
D;D;D;D;D
Sift4G
Benign
0.096
T;T;T;.;T
Polyphen
1.0
D;.;D;D;D
Vest4
0.63
MutPred
0.47
Loss of MoRF binding (P = 0.2355);Loss of MoRF binding (P = 0.2355);Loss of MoRF binding (P = 0.2355);.;.;
MVP
0.56
MPC
2.8
ClinPred
0.58
D
GERP RS
5.5
Varity_R
0.13
gMVP
0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760054653; hg19: chr3-49898427; API