chr3-49859458-C-A

Variant names:

• chr3-49859458-C-A
• rs1259989462
• NM_024046.5:c.1366G>T

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.1366G>T​(p.Ala456Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.236
• 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=0.0783951).

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.1366G>T	p.Ala456Ser	missense	Exon 11 of 11	NP_076951.2	Q8NCB2-1
	CAMKV	NM_001320147.2		c.1273G>T	p.Ala425Ser	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.1366G>T	p.Ala456Ser	missense	Exon 11 of 11	ENSP00000419195.1	Q8NCB2-1
	CAMKV	ENST00000296471.11	TSL:1	c.1282G>T	p.Ala428Ser	missense	Exon 10 of 10	ENSP00000296471.6	Q8NCB2-2
	CAMKV	ENST00000620470.4	TSL:1	c.1282G>T	p.Ala428Ser	missense	Exon 9 of 9	ENSP00000484045.1	Q8NCB2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461586 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727056

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

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.0086
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.24
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.057
Sift	Benign	0.056	T
Sift4G	Benign	0.16	T
Polyphen		0.0020	B
Vest4		0.078
MutPred		0.14		Loss of glycosylation at K455 (P = 0.0349)
MVP		0.49
MPC		0.71
ClinPred		0.21	T
GERP RS		4.1
Varity_R		0.065
gMVP		0.11
Mutation Taster		=75/25	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: rs1259989462; hg19: chr3-49896891;