chr6-36742414-C-T

Variant summary

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

The NM_020939.2(CPNE5):​c.1636G>A​(p.Val546Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CPNE5
NM_020939.2 missense

Scores

8
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46
Variant links:
Genes affected
CPNE5 (HGNC:2318): (copine 5) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

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
CPNE5NM_020939.2 linkc.1636G>A p.Val546Met missense_variant Exon 21 of 21 ENST00000244751.7 NP_065990.1 Q9HCH3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPNE5ENST00000244751.7 linkc.1636G>A p.Val546Met missense_variant Exon 21 of 21 1 NM_020939.2 ENSP00000244751.2 Q9HCH3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250882
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461420
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727068
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1636G>A (p.V546M) alteration is located in exon 21 (coding exon 21) of the CPNE5 gene. This alteration results from a G to A substitution at nucleotide position 1636, causing the valine (V) at amino acid position 546 to be replaced by a methionine (M). 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
Pathogenic
0.98
BayesDel_addAF
Benign
-0.020
T
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.5
.;H
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
.;D
Vest4
0.68
MutPred
0.46
.;Gain of disorder (P = 0.0813);
MVP
0.54
MPC
1.7
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.75
gMVP
0.89

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: rs1186376904; hg19: chr6-36710191; API