3-62438139-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003716.4(CADPS):​c.3742G>A​(p.Val1248Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. V1248F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CADPS
NM_003716.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.11
Variant links:
Genes affected
CADPS (HGNC:1426): (calcium dependent secretion activator) This gene encodes a novel neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+-regulated exocytosis of secretory vesicles. The protein acts at a stage in exocytosis that follows ATP-dependent priming, which involves the essential synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Alternative splicing has been observed at this locus and three variants, encoding distinct isoforms, are described. [provided by RefSeq, Aug 2008]

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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=0.24430716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CADPSNM_003716.4 linkc.3742G>A p.Val1248Ile missense_variant Exon 28 of 30 ENST00000383710.9 NP_003707.2 Q9ULU8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CADPSENST00000383710.9 linkc.3742G>A p.Val1248Ile missense_variant Exon 28 of 30 1 NM_003716.4 ENSP00000373215.4 Q9ULU8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Pathogenic
27
DANN
Benign
0.97
DEOGEN2
Benign
0.010
T;T;.;.;.
Eigen
Benign
0.075
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;D;D;D;D
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;L;.;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.45
.;N;N;.;N
REVEL
Benign
0.068
Sift
Benign
0.45
.;T;T;.;T
Sift4G
Benign
0.56
T;T;T;T;T
Polyphen
0.0020, 0.084, 0.0010
.;B;B;.;B
Vest4
0.25
MutPred
0.22
.;Gain of glycosylation at Y1253 (P = 0.0378);.;.;.;
MVP
0.40
MPC
0.58
ClinPred
0.71
D
GERP RS
5.7
Varity_R
0.14
gMVP
0.083

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751860249; hg19: chr3-62423814; COSMIC: COSV99340661; API