Genetic Variant NM_024046.5:c.1481A>C (chr3-49859343-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024046.5(CAMKV):c.1481A>C(p.Glu494Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E494V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CAMKV
NM_024046.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

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]

CAMKV links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116019666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5 link	c.1481A>C	p.Glu494Ala	missense_variant	Exon 11 of 11	ENST00000477224.6	NP_076951.2	Q8NCB2-1A0A140VKD5
CAMKV	NM_001320147.2 link	c.1388A>C	p.Glu463Ala	missense_variant	Exon 12 of 12		NP_001307076.1	Q8NCB2-3A0A024R331

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6 link	c.1481A>C	p.Glu494Ala	missense_variant	Exon 11 of 11	1	NM_024046.5	ENSP00000419195.1		Q8NCB2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000508

AC:

AN:

196832

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.00

AC:

AN:

36316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21198

East Asian (EAS)

AF:

0.00

AC:

AN:

39066

South Asian (SAS)

AF:

0.00

AC:

AN:

73902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5206

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1074990

Other (OTH)

AF:

0.00

AC:

AN:

57230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

.;.;T;.;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

.;D;D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.55

.;.;N;.;.;.

PhyloP100

0.15

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.60

N;N;N;.;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;.;D;D

Sift4G

Benign

0.36

T;D;D;T;.;D

Polyphen

0.50

P;B;B;P;P;B

Vest4

0.12

MutPred

0.17

.;.;Gain of glycosylation at Y491 (P = 0);.;.;.;

MVP

0.58

MPC

1.9

ClinPred

0.47

GERP RS

4.2

Varity_R

0.19

gMVP

0.21

Mutation Taster

=75/25

polymorphism

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over