3-62765942-C-T

Variant names:

• chr3-62765942-C-T
• rs193921128
• NM_003716.4:c.484G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003716.4(CADPS):​c.484G>A​(p.Ala162Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CADPS NM_003716.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003716.4. 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
	CADPS	NM_003716.4	MANE Select	c.484G>A	p.Ala162Thr	missense	Exon 2 of 30	NP_003707.2
	CADPS	NM_001438347.1		c.484G>A	p.Ala162Thr	missense	Exon 2 of 31	NP_001425276.1
	CADPS	NM_001438348.1		c.484G>A	p.Ala162Thr	missense	Exon 2 of 30	NP_001425277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS	ENST00000383710.9	TSL:1 MANE Select	c.484G>A	p.Ala162Thr	missense	Exon 2 of 30	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.484G>A	p.Ala162Thr	missense	Exon 2 of 28	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.484G>A	p.Ala162Thr	missense	Exon 2 of 28	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.7	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.78	P
Vest4		0.72
MutPred		0.22		Gain of methylation at K157 (P = 0.1104)
MVP		0.83
MPC		0.92
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.31
gMVP		0.072
Mutation Taster		=38/62	disease causing

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: rs193921128; hg19: chr3-62751617; COSMIC: COSV51892951;