dbSNP rs778427920: CAMKV:p.Ala475Ser (chr3-49859401-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024046.5(CAMKV):c.1423G>T(p.Ala475Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A475T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CAMKV
NM_024046.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

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: 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=0.03871733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5 link	c.1423G>T	p.Ala475Ser	missense_variant	Exon 11 of 11	ENST00000477224.6	NP_076951.2	Q8NCB2-1A0A140VKD5
CAMKV	NM_001320147.2 link	c.1330G>T	p.Ala444Ser	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.1423G>T	p.Ala475Ser	missense_variant	Exon 11 of 11	1	NM_024046.5	ENSP00000419195.1		Q8NCB2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33216

American (AMR)

AF:

0.00

AC:

AN:

44072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25200

East Asian (EAS)

AF:

0.00

AC:

AN:

39454

South Asian (SAS)

AF:

0.00

AC:

AN:

84520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102084

Other (OTH)

AF:

0.00

AC:

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.2

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.074

.;.;T;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.80

.;T;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.039

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;.;N;.;.;.

PhyloP100

-1.9

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.29

N;N;N;.;N;N

REVEL

Benign

0.046

Sift

Uncertain

0.023

D;D;D;.;D;D

Sift4G

Benign

0.069

T;T;T;T;.;T

Polyphen

0.034

B;B;B;B;B;B

Vest4

0.043

MutPred

0.077

.;.;Loss of glycosylation at P480 (P = 0.0224);.;.;.;

MVP

0.46

MPC

0.74

ClinPred

0.065

GERP RS

-5.6

Varity_R

0.036

gMVP

0.057

Mutation Taster

=95/5

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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rs778427920

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over