3-49859569-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.708
Variant links:
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]

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ACMG classification

Classification made for transcript

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
CAMKVNM_024046.5 linkc.1255A>T p.Thr419Ser missense_variant Exon 11 of 11 ENST00000477224.6 NP_076951.2 Q8NCB2-1A0A140VKD5
CAMKVNM_001320147.2 linkc.1162A>T p.Thr388Ser missense_variant Exon 12 of 12 NP_001307076.1 Q8NCB2-3A0A024R331

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAMKVENST00000477224.6 linkc.1255A>T p.Thr419Ser missense_variant Exon 11 of 11 1 NM_024046.5 ENSP00000419195.1 Q8NCB2-1

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
LINK: link

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; API