Variant 12-38767656-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000331366.10(CPNE8):c.554A>G(p.Tyr185Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000354 in 1,410,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CPNE8
ENST00000331366.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

Variant links:

Genes affected

CPNE8 (HGNC:23498): (copine 8) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. [provided by RefSeq, Jul 2008]

CPNE8 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	Protein	UniProt
CPNE8	NM_153634.3 linkuse as main transcript	c.554A>G	p.Tyr185Cys	missense_variant	8/20	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10 linkuse as main transcript	c.554A>G	p.Tyr185Cys	missense_variant	8/20	1	NM_153634.3	ENSP00000329748	P1	Q86YQ8-1
CPNE8	ENST00000360449.3 linkuse as main transcript	c.518A>G	p.Tyr173Cys	missense_variant	8/20	2		ENSP00000353633
CPNE8	ENST00000551855.1 linkuse as main transcript	n.62A>G		non_coding_transcript_exon_variant	1/5	3
CPNE8	ENST00000550863.1 linkuse as main transcript			downstream_gene_variant		4		ENSP00000447761

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000955

AC:

AN:

209436

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000718

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000208

GnomAD4 exome

AF:

0.00000354

AC:

AN:

1410792

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000685

GnomAD4 genome

Cov.:

Alfa

AF:

0.000223

Hom.:

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

Mar 29, 2024

The c.554A>G (p.Y185C) alteration is located in exon 8 (coding exon 8) of the CPNE8 gene. This alteration results from a A to G substitution at nucleotide position 554, causing the tyrosine (Y) at amino acid position 185 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.051

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Benign

0.21

Sift

Benign

0.054

T;T

Sift4G

Uncertain

0.055

T;T

Polyphen

0.030

B;.

Vest4

0.83

MutPred

0.62

Gain of sheet (P = 0.1539);.;

MVP

0.60

MPC

1.1

ClinPred

0.88

GERP RS

4.4

Varity_R

0.44

gMVP

0.62

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