3-49859377-T-C

Variant names:

• chr3-49859377-T-C
• rs1011785677
• NM_024046.5:c.1447A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024046.5(CAMKV):​c.1447A>G​(p.Ser483Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,576,314 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.869

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.089239776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.1447A>G	p.Ser483Gly	missense_variant	Exon 11 of 11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.1354A>G	p.Ser452Gly	missense_variant	Exon 12 of 12		NP_001307076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMKV	ENST00000477224.6	c.1447A>G	p.Ser483Gly	missense_variant	Exon 11 of 11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226352 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000183

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424134 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 703398

African (AFR) AF: 0.00 AC: 0 AN: 32738

American (AMR) AF: 0.0000477 AC: 2 AN: 41956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23488

East Asian (EAS) AF: 0.00 AC: 0 AN: 39276

South Asian (SAS) AF: 0.00 AC: 0 AN: 80512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51670

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090276

Other (OTH) AF: 0.00 AC: 0 AN: 58716

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1447A>G (p.S483G) alteration is located in exon 11 (coding exon 10) of the CAMKV gene. This alteration results from a A to G substitution at nucleotide position 1447, causing the serine (S) at amino acid position 483 to be replaced by a glycine (G). 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	Benign	0.062
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Benign	0.64
DEOGEN2	Benign	0.052	.;.;T;.;T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.84	.;T;D;D;D;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.089	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	.;.;N;.;.;.
PhyloP100		0.87
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.66	N;N;N;.;N;N
REVEL	Benign	0.061
Sift	Uncertain	0.013	D;D;D;.;D;D
Sift4G	Benign	0.35	T;T;T;T;.;T
Polyphen		0.0	B;B;B;B;B;B
Vest4		0.19
MutPred		0.12		.;.;Loss of glycosylation at P481 (P = 0.0092);.;.;.;
MVP		0.55
MPC		0.79
ClinPred		0.080	T
GERP RS		1.2
Varity_R		0.045
gMVP		0.15
Mutation Taster		=91/9	polymorphism

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: rs1011785677; hg19: chr3-49896810;