chr14-24075839-C-T

Position:

• chr14-24075839-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006032.4(CPNE6):​c.877C>T​(p.His293Tyr) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

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]

CPNE6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08318955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE6	NM_006032.4	c.877C>T	p.His293Tyr	missense_variant	10/17	ENST00000689861.1	NP_006023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE6	ENST00000689861.1	c.877C>T	p.His293Tyr	missense_variant	10/17		NM_006032.4	ENSP00000510387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jun 07, 2024

The c.877C>T (p.H293Y) alteration is located in exon 10 (coding exon 9) of the CPNE6 gene. This alteration results from a C to T substitution at nucleotide position 877, causing the histidine (H) at amino acid position 293 to be replaced by a tyrosine (Y). 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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Benign	0.045	.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.68	.;N
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	2.6	N;N
REVEL	Benign	0.078
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	.;B
Vest4		0.19
MutPred		0.64		.;Gain of catalytic residue at D297 (P = 0.0084);
MVP		0.23
MPC		0.72
ClinPred		0.24	T
GERP RS		5.0
Varity_R		0.057
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24545048;