Genetic Variant CAMKV:p.Gly9Gly (chr3-49862362-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024046.5(CAMKV):c.27C>T(p.Gly9Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,613,286 control chromosomes in the GnomAD database, including 124,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10490 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113604 hom. )

Consequence

CAMKV
NM_024046.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.41

Publications

27 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-49862362-G-A is Benign according to our data. Variant chr3-49862362-G-A is described in ClinVar as Benign. ClinVar VariationId is 1270206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5 link	c.27C>T	p.Gly9Gly	synonymous_variant	Exon 2 of 11	ENST00000477224.6	NP_076951.2	Q8NCB2-1A0A140VKD5
CAMKV	NM_001320147.2 link	c.27C>T	p.Gly9Gly	synonymous_variant	Exon 2 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.27C>T	p.Gly9Gly	synonymous_variant	Exon 2 of 11	1	NM_024046.5	ENSP00000419195.1		Q8NCB2-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55180

AN:

151946

Hom.:

10485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.366

GnomAD2 exomes

AF:

0.321

AC:

80770

AN:

251422

AF XY:

0.322

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.385

AC:

562747

AN:

1461222

Hom.:

113604

Cov.:

AF XY:

0.380

AC XY:

276438

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.356

AC:

11905

AN:

33468

American (AMR)

AF:

0.251

AC:

11216

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

7032

AN:

26130

East Asian (EAS)

AF:

0.133

AC:

5285

AN:

39700

South Asian (SAS)

AF:

0.173

AC:

14935

AN:

86248

European-Finnish (FIN)

AF:

0.321

AC:

17101

AN:

53354

Middle Eastern (MID)

AF:

0.351

AC:

2025

AN:

5768

European-Non Finnish (NFE)

AF:

0.424

AC:

471027

AN:

1111452

Other (OTH)

AF:

0.368

AC:

22221

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

19155

38309

57464

76618

95773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14090

28180

42270

56360

70450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55205

AN:

152064

Hom.:

10490

Cov.:

AF XY:

0.354

AC XY:

26320

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.360

AC:

14934

AN:

41432

American (AMR)

AF:

0.328

AC:

5017

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3468

East Asian (EAS)

AF:

0.118

AC:

612

AN:

5166

South Asian (SAS)

AF:

0.166

AC:

803

AN:

4830

European-Finnish (FIN)

AF:

0.316

AC:

3341

AN:

10580

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28308

AN:

67988

Other (OTH)

AF:

0.369

AC:

779

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1827

3655

5482

7310

9137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.390

Hom.:

10542

Bravo

AF:

0.369

Asia WGS

AF:

0.205

AC:

712

AN:

3478

EpiCase

AF:

0.414

EpiControl

AF:

0.418

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 08, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.31

(source)

DANN

Benign

0.80

PhyloP100

-2.4

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.020

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

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over