Variant 16-89583444-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000268720.9(CPNE7):c.498G>C(p.Arg166Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,550,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CPNE7
ENST00000268720.9 missense, splice_region

Scores

Splicing: ADA: 0.9272

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.140

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:

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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.358-253G>C		intron_variant		ENST00000319518.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE7	ENST00000268720.9 linkuse as main transcript	c.498G>C	p.Arg166Ser	missense_variant, splice_region_variant	4/17	1			Q9UBL6-1
CPNE7	ENST00000319518.13 linkuse as main transcript	c.358-253G>C		intron_variant		1	NM_153636.3	P1	Q9UBL6-2
CPNE7	ENST00000525982.5 linkuse as main transcript	c.358G>C	p.Val120Leu	missense_variant, splice_region_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

156182

Hom.:

AF XY:

0.0000364

AC XY:

AN XY:

82316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

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:

0.0000664

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000601

AC:

AN:

1398090

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

689608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.0000760

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000151

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

Oct 27, 2022

The c.498G>C (p.R166S) alteration is located in exon 4 (coding exon 4) of the CPNE7 gene. This alteration results from a G to C substitution at nucleotide position 498, causing the arginine (R) at amino acid position 166 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.86

DEOGEN2

Benign

0.035

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.25

M_CAP

Benign

0.0019

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.14

REVEL

Benign

0.087

Sift

Pathogenic

0.0

Sift4G

Benign

0.73

Polyphen

0.0060

Vest4

0.20

MutPred

0.49

Loss of stability (P = 0.0511);

MVP

0.33

MPC

0.066

ClinPred

0.074

GERP RS

1.3

Varity_R

0.28

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Pathogenic

0.73

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.38

Position offset: -9

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