3-62474310-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003716.4(CADPS):​c.3340G>T​(p.Ala1114Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A1114T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

CADPS
NM_003716.4 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CADPSNM_003716.4 linkc.3340G>T p.Ala1114Ser missense_variant Exon 24 of 30 ENST00000383710.9 NP_003707.2 Q9ULU8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CADPSENST00000383710.9 linkc.3340G>T p.Ala1114Ser missense_variant Exon 24 of 30 1 NM_003716.4 ENSP00000373215.4 Q9ULU8-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251032
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.029
T;T;.;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.9
.;L;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-1.7
.;N;N;N
REVEL
Benign
0.21
Sift
Benign
0.32
.;T;T;T
Sift4G
Benign
0.29
T;T;T;T
Polyphen
1.0, 0.68, 1.0
.;D;P;D
Vest4
0.74
MutPred
0.37
.;Gain of glycosylation at T1111 (P = 0.0197);.;.;
MVP
0.44
MPC
0.78
ClinPred
0.83
D
GERP RS
5.2
Varity_R
0.23
gMVP
0.044

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs781377421; hg19: chr3-62459985; API