Genetic Variant CPNE6:p.Leu63Ile (chr14-24073517-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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)

Consequence

CPNE6
NM_006032.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Publications

0 publications found

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]

CPNE6 links:

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

DHRS4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035761207).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE6	NM_006032.4	MANE Select	c.187C>A	p.Leu63Ile	missense	Exon 3 of 17	NP_006023.1	O95741-1
CPNE6	NM_001280558.2		c.352C>A	p.Leu118Ile	missense	Exon 4 of 18	NP_001267487.1	O95741-2
CPNE6	NM_001385056.1		c.187C>A	p.Leu63Ile	missense	Exon 4 of 18	NP_001371985.1	O95741-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE6	ENST00000689861.1	MANE Select	c.187C>A	p.Leu63Ile	missense	Exon 3 of 17	ENSP00000510387.1	O95741-1
CPNE6	ENST00000537691.5	TSL:2	c.352C>A	p.Leu118Ile	missense	Exon 4 of 18	ENSP00000440077.1	O95741-2
CPNE6	ENST00000966862.1		c.220C>A	p.Leu74Ile	missense	Exon 3 of 17	ENSP00000636921.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251092

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.083

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.0037

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.8

PhyloP100

2.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

1.5

REVEL

Benign

0.063

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.14

MVP

0.24

MPC

0.67

ClinPred

0.13

GERP RS

2.4

Varity_R

0.062

gMVP

0.097

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over