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
• Publications: 0 publications found

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKV	NM_024046.5	MANE Select	c.1320G>C	p.Glu440Asp	missense	Exon 11 of 11	NP_076951.2	Q8NCB2-1
	CAMKV	NM_001320147.2		c.1227G>C	p.Glu409Asp	missense	Exon 12 of 12	NP_001307076.1	Q8NCB2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMKV	ENST00000477224.6	TSL:1 MANE Select	c.1320G>C	p.Glu440Asp	missense	Exon 11 of 11	ENSP00000419195.1	Q8NCB2-1
	CAMKV	ENST00000296471.11	TSL:1	c.1236G>C	p.Glu412Asp	missense	Exon 10 of 10	ENSP00000296471.6	Q8NCB2-2
	CAMKV	ENST00000620470.4	TSL:1	c.1236G>C	p.Glu412Asp	missense	Exon 9 of 9	ENSP00000484045.1	Q8NCB2-2

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 v4.9

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
Eigen	Benign	-0.016
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.41
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D
Sift4G	Benign	0.42	T
Polyphen		0.75	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

Other links and lift over

dbSNP: rs144523890; hg19: chr3-49896937;