14-24073517-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006032.4(CPNE6):​c.187C>A​(p.Leu63Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CPNE6
NM_006032.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42
Variant links:
Genes affected
CPNE6 (HGNC:2319): (copine 6) This gene encodes a member of the copine family. Members of this family are calcium-dependent, phospholipid-binding proteins with C2 domains, two calcium- and phospholipid-binding domains. Through their domain structure and lipid binding capabilities, these proteins may play a role in membrane trafficking. This protein is thought to be brain-specific and has a domain structure of two N-terminal C2 domains and one von Willebrand factor A domain. It may have a role in synaptic plasticity. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.035761207).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPNE6NM_006032.4 linkc.187C>A p.Leu63Ile missense_variant Exon 3 of 17 ENST00000689861.1 NP_006023.1 O95741-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPNE6ENST00000689861.1 linkc.187C>A p.Leu63Ile missense_variant Exon 3 of 17 NM_006032.4 ENSP00000510387.1 O95741-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251092
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135728
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.187C>A (p.L63I) alteration is located in exon 3 (coding exon 2) of the CPNE6 gene. This alteration results from a C to A substitution at nucleotide position 187, causing the leucine (L) at amino acid position 63 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Benign
0.80
DEOGEN2
Benign
0.083
.;T;T;T;T;.;.;T;.;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.54
D
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.036
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-1.8
.;N;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
1.5
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.063
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T;T;T
Polyphen
0.0
.;B;.;.;.;.;.;.;.;.
Vest4
0.14
MVP
0.24
MPC
0.67
ClinPred
0.13
T
GERP RS
2.4
Varity_R
0.062
gMVP
0.097

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs150745012; hg19: chr14-24542726; API