Variant 3-62474171-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003716.4(CADPS):c.3477+2T>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00065 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CADPS
NM_003716.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Variant links:

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]

CADPS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS	NM_003716.4 link	c.3477+2T>A		splice_donor_variant, intron_variant	Intron 24 of 29	ENST00000383710.9	NP_003707.2	Q9ULU8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS	ENST00000383710.9 link	c.3477+2T>A		splice_donor_variant, intron_variant	Intron 24 of 29	1	NM_003716.4	ENSP00000373215.4		Q9ULU8-1

Frequencies

GnomAD3 genomes

AF:

0.00713

AC:

125

AN:

17522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00948

Gnomad AMI

AF:

0.0141

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00183

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.00177

Gnomad FIN

AF:

0.00740

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.00769

Gnomad OTH

AF:

0.00407

GnomAD3 exomes

AF:

0.00152

AC:

AN:

36068

Hom.:

AF XY:

0.00151

AC XY:

AN XY:

19154

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00251

Gnomad EAS exome

AF:

0.00190

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00241

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000655

AC:

258

AN:

394036

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

138

AN XY:

198820

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00118

Gnomad4 ASJ exome

AF:

0.000788

Gnomad4 EAS exome

AF:

0.000514

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.00102

Gnomad4 NFE exome

AF:

0.000553

Gnomad4 OTH exome

AF:

0.000628

GnomAD4 genome

AF:

0.00713

AC:

125

AN:

17522

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

AN XY:

8782

show subpopulations

Gnomad4 AFR

AF:

0.00945

Gnomad4 AMR

AF:

0.00459

Gnomad4 ASJ

AF:

0.00183

Gnomad4 EAS

AF:

0.00427

Gnomad4 SAS

AF:

0.00177

Gnomad4 FIN

AF:

0.00740

Gnomad4 NFE

AF:

0.00768

Gnomad4 OTH

AF:

0.00400

ExAC

AF:

0.00180

AC:

211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.99

GERP RS

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.73

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.73

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over