3-62765942-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003716.4(CADPS):​c.484G>T​(p.Ala162Ser) 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. 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. A162T) 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: 6.00
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3088371).

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>T	p.Ala162Ser	missense	Exon 2 of 30	NP_003707.2
	CADPS	NM_001438347.1		c.484G>T	p.Ala162Ser	missense	Exon 2 of 31	NP_001425276.1
	CADPS	NM_001438348.1		c.484G>T	p.Ala162Ser	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>T	p.Ala162Ser	missense	Exon 2 of 30	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.484G>T	p.Ala162Ser	missense	Exon 2 of 28	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.484G>T	p.Ala162Ser	missense	Exon 2 of 28	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.095	N
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.36
Sift	Benign	0.59	T
Sift4G	Benign	0.86	T
Polyphen		0.087	B
Vest4		0.52
MutPred		0.22		Gain of disorder (P = 0.0511)
MVP		0.69
MPC		0.78
ClinPred		0.80	D
GERP RS		5.2
Varity_R		0.22
gMVP		0.051
Mutation Taster		=47/53	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;