3-49859504-C-G

Variant names:

• chr3-49859504-C-G
• rs144523890
• NM_024046.5:c.1320G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024046.5(CAMKV):​c.1320G>C​(p.Glu440Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

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: 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=0.084130704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.1320G>C	p.Glu440Asp	missense_variant	Exon 11 of 11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.1227G>C	p.Glu409Asp	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.1320G>C	p.Glu440Asp	missense_variant	Exon 11 of 11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	.;.;T;.;T;T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.72	.;T;T;T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.
PhyloP100		0.41
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.48	N;N;N;.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D;D;D;.;D;D
Sift4G	Benign	0.42	T;T;T;T;.;T
Polyphen		0.75	P;P;P;P;D;P
Vest4		0.062
MutPred		0.10		.;.;Loss of glycosylation at T445 (P = 0.0621);.;.;.;
MVP		0.50
MPC		0.70
ClinPred		0.32	T
GERP RS		4.5
Varity_R		0.084
gMVP		0.054
Mutation Taster		=88/12	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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs144523890; hg19: chr3-49896937;