3-49859401-C-A

Variant names:

• chr3-49859401-C-A
• rs778427920
• NM_024046.5:c.1423G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024046.5(CAMKV):​c.1423G>T​(p.Ala475Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,598 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A475T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03871733).

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.1423G>T	p.Ala475Ser	missense	Exon 11 of 11	NP_076951.2	Q8NCB2-1
	CAMKV	NM_001320147.2		c.1330G>T	p.Ala444Ser	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.1423G>T	p.Ala475Ser	missense	Exon 11 of 11	ENSP00000419195.1	Q8NCB2-1
	CAMKV	ENST00000296471.11	TSL:1	c.1339G>T	p.Ala447Ser	missense	Exon 10 of 10	ENSP00000296471.6	Q8NCB2-2
	CAMKV	ENST00000620470.4	TSL:1	c.1339G>T	p.Ala447Ser	missense	Exon 9 of 9	ENSP00000484045.1	Q8NCB2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446598 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 717302

African (AFR) AF: 0.00 AC: 0 AN: 33216

American (AMR) AF: 0.00 AC: 0 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25200

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 84520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102084

Other (OTH) AF: 0.00 AC: 0 AN: 59620

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.2
DANN	Benign	0.82
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.9
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.046
Sift	Uncertain	0.023	D
Sift4G	Benign	0.069	T
Polyphen		0.034	B
Vest4		0.043
MutPred		0.077		Loss of glycosylation at P480 (P = 0.0224)
MVP		0.46
MPC		0.74
ClinPred		0.065	T
GERP RS		-5.6
Varity_R		0.036
gMVP		0.057
Mutation Taster		=95/5	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: rs778427920; hg19: chr3-49896834;