3-62438139-C-T

Variant names:

• chr3-62438139-C-T
• rs751860249
• NM_003716.4:c.3742G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11

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]

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=0.24430716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4	c.3742G>A	p.Val1248Ile	missense_variant	Exon 28 of 30	ENST00000383710.9	NP_003707.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9	c.3742G>A	p.Val1248Ile	missense_variant	Exon 28 of 30	1	NM_003716.4	ENSP00000373215.4

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

Other links and lift over

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