3-62399451-G-A

Variant names:

• chr3-62399451-G-A
• rs779869772
• NM_003716.4:c.4017C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_003716.4(CADPS):​c.4017C>T​(p.Gly1339Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G1339G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CADPS NM_003716.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• 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
• BP7: Synonymous conserved (PhyloP=-2.53 with no splicing effect.

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.4017C>T	p.Gly1339Gly	synonymous	Exon 30 of 30	NP_003707.2
	CADPS	NM_001438347.1		c.4077C>T	p.Gly1359Gly	synonymous	Exon 31 of 31	NP_001425276.1
	CADPS	NM_001438348.1		c.4065C>T	p.Gly1355Gly	synonymous	Exon 30 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.4017C>T	p.Gly1339Gly	synonymous	Exon 30 of 30	ENSP00000373215.4	Q9ULU8-1
	CADPS	ENST00000612439.4	TSL:1	c.3990C>T	p.Gly1330Gly	synonymous	Exon 28 of 28	ENSP00000484365.1	F1T0E5
	CADPS	ENST00000283269.13	TSL:1	c.3900C>T	p.Gly1300Gly	synonymous	Exon 28 of 28	ENSP00000283269.9	Q9ULU8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.66
DANN	Benign	0.77
PhyloP100		-2.5

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: rs779869772; hg19: chr3-62385126;