14-24073600-C-A

Variant names:

• chr14-24073600-C-A
• rs565232023
• NM_006032.4:c.270C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006032.4(CPNE6):​c.270C>A​(p.His90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • 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: -3.67
• Publications: 0 publications found

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]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1473284).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006032.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE6	NM_006032.4	MANE Select	c.270C>A	p.His90Gln	missense	Exon 3 of 17	NP_006023.1	O95741-1
	CPNE6	NM_001280558.2		c.435C>A	p.His145Gln	missense	Exon 4 of 18	NP_001267487.1	O95741-2
	CPNE6	NM_001385056.1		c.270C>A	p.His90Gln	missense	Exon 4 of 18	NP_001371985.1	O95741-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE6	ENST00000689861.1	MANE Select	c.270C>A	p.His90Gln	missense	Exon 3 of 17	ENSP00000510387.1	O95741-1
	CPNE6	ENST00000537691.5	TSL:2	c.435C>A	p.His145Gln	missense	Exon 4 of 18	ENSP00000440077.1	O95741-2
	CPNE6	ENST00000966862.1		c.303C>A	p.His101Gln	missense	Exon 3 of 17	ENSP00000636921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.56
DANN	Benign	0.89
DEOGEN2	Benign	0.083	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.054	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.17	N
PhyloP100		-3.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.15
Sift	Benign	0.30	T
Sift4G	Benign	0.32	T
Polyphen		0.31	B
Vest4		0.50
MutPred		0.52		Gain of catalytic residue at F92 (P = 0.0091)
MVP		0.72
MPC		0.64
ClinPred		0.43	T
GERP RS		-4.0
Varity_R		0.049
gMVP		0.29
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs565232023; hg19: chr14-24542809;