14-24076548-G-C

Position:

• chr14-24076548-G-C

Variant summary

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

The NM_006032.4(CPNE6):​c.1156G>C​(p.Glu386Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPNE6 NM_006032.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

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]

ACMG classification

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/exons	MANE	Protein	UniProt
CPNE6	NM_006032.4	c.1156G>C	p.Glu386Gln	missense_variant	13/17	ENST00000689861.1	NP_006023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE6	ENST00000689861.1	c.1156G>C	p.Glu386Gln	missense_variant	13/17		NM_006032.4	ENSP00000510387	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.1156G>C (p.E386Q) alteration is located in exon 13 (coding exon 12) of the CPNE6 gene. This alteration results from a G to C substitution at nucleotide position 1156, causing the glutamic acid (E) at amino acid position 386 to be replaced by a glutamine (Q). 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	0.22
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.5	.;M
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.22
Sift	Benign	0.27	T;T
Sift4G	Benign	0.27	T;T
Polyphen		1.0	.;D
Vest4		0.47
MutPred		0.53		.;Gain of catalytic residue at D381 (P = 0.002);
MVP		0.56
MPC		1.4
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24545757;