rs771045473

Variant names:

• chr3-62438196-C-A
• rs771045473
• NM_003716.4:c.3685G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-62438196-C-A
• chr3-62438196-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003716.4(CADPS):​c.3685G>T​(p.Val1229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,250 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (1 hom.)
• Consequence: CADPS NM_003716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.27
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018928647).

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.3685G>T	p.Val1229Leu	missense	Exon 28 of 30	NP_003707.2
	CADPS	NM_001438347.1		c.3745G>T	p.Val1249Leu	missense	Exon 29 of 31	NP_001425276.1
	CADPS	NM_001438348.1		c.3733G>T	p.Val1245Leu	missense	Exon 28 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.3685G>T	p.Val1229Leu	missense	Exon 28 of 30	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.3658G>T	p.Val1220Leu	missense	Exon 26 of 28	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.3568G>T	p.Val1190Leu	missense	Exon 26 of 28	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000167 AC: 42 AN: 250844 AF XY: 0.000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1460956 Hom.: 1 Cov.: 30 AF XY: 0.0000605 AC XY: 44 AN XY: 726850

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.000958 AC: 38 AN: 39686

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111278

Other (OTH) AF: 0.000149 AC: 9 AN: 60328

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000438 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CADPS-related disorder (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.61
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.40	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.95	P
Vest4		0.41
MutPred		0.21		Gain of glycosylation at Y1233 (P = 0.0056)
MVP		0.42
MPC		0.52
ClinPred		0.060	T
GERP RS		5.7
Varity_R		0.21
gMVP		0.13
Mutation Taster		=92/8	polymorphism

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: rs771045473; hg19: chr3-62423871;