Variant 16-89584825-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153636.3(CPNE7):c.559G>A(p.Asp187Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CPNE7
NM_153636.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.31

Variant links:

Genes affected

CPNE7 (HGNC:2320): (copine 7) This gene encodes a member of the copine family, which is composed of calcium-dependent membrane-binding proteins. The gene product contains two N-terminal C2 domains and one von Willebrand factor A domain. The encoded protein may be involved in membrane trafficking. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

CPNE7 links:

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/exons	MANE	UniProt
CPNE7	NM_153636.3 linkuse as main transcript	c.559G>A	p.Asp187Asn	missense_variant	5/15	ENST00000319518.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE7	ENST00000319518.13 linkuse as main transcript	c.559G>A	p.Asp187Asn	missense_variant	5/15	1	NM_153636.3	P1	Q9UBL6-2
CPNE7	ENST00000268720.9 linkuse as main transcript	c.784G>A	p.Asp262Asn	missense_variant	7/17	1			Q9UBL6-1
CPNE7	ENST00000532500.1 linkuse as main transcript	n.5G>A		non_coding_transcript_exon_variant	1/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250264

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461314

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.784G>A (p.D262N) alteration is located in exon 7 (coding exon 7) of the CPNE7 gene. This alteration results from a G to A substitution at nucleotide position 784, causing the aspartic acid (D) at amino acid position 262 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

0.031

Eigen_PC

Benign

-0.056

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.23

Sift

Benign

0.048

D;T

Sift4G

Uncertain

0.058

T;T

Polyphen

0.93

P;P

Vest4

0.57

MutPred

0.54

Gain of sheet (P = 0.1208);.;

MVP

0.71

MPC

0.31

ClinPred

0.95

GERP RS

3.8

Varity_R

0.34

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over