3-49859569-T-A

Variant names:

• chr3-49859569-T-A
• NM_024046.5:c.1255A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024046.5(CAMKV):​c.1255A>T​(p.Thr419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: CAMKV NM_024046.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.708

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11241743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMKV	NM_024046.5	c.1255A>T	p.Thr419Ser	missense_variant	Exon 11 of 11	ENST00000477224.6	NP_076951.2
CAMKV	NM_001320147.2	c.1162A>T	p.Thr388Ser	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.1255A>T	p.Thr419Ser	missense_variant	Exon 11 of 11	1	NM_024046.5	ENSP00000419195.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1255A>T (p.T419S) alteration is located in exon 11 (coding exon 10) of the CAMKV gene. This alteration results from a A to T substitution at nucleotide position 1255, causing the threonine (T) at amino acid position 419 to be replaced by a serine (S). 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	0.079
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.060	.;.;T;.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	.;T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	.;.;N;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.32	N;N;N;.;N;N
REVEL	Benign	0.084
Sift	Benign	0.22	T;T;T;.;T;T
Sift4G	Benign	0.18	T;T;T;T;.;T
Polyphen		0.020	B;B;B;B;B;B
Vest4		0.11
MutPred		0.059		.;.;Loss of glycosylation at T419 (P = 0.1541);.;.;.;
MVP		0.57
MPC		1.7
ClinPred		0.62	D
GERP RS		5.3
Varity_R		0.059
gMVP		0.071

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49897002;