dbSNP rs369822693: CPNE8:p.Gly54Val (chr12-38873029-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153634.3(CPNE8):c.161G>T(p.Gly54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G54A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CPNE8
NM_153634.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.22203285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153634.3. 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
	CPNE8	NM_153634.3	MANE Select	c.161G>T	p.Gly54Val	missense	Exon 3 of 20	NP_705898.1	Q86YQ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.161G>T	p.Gly54Val	missense	Exon 3 of 20	ENSP00000329748.5	Q86YQ8-1
CPNE8	ENST00000360449.3	TSL:2	c.125G>T	p.Gly42Val	missense	Exon 3 of 20	ENSP00000353633.3	E7ENV7
CPNE8	ENST00000862791.1		c.161G>T	p.Gly54Val	missense	Exon 3 of 20	ENSP00000532850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1403426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700874

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31676

American (AMR)

AF:

0.00

AC:

AN:

42618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25586

East Asian (EAS)

AF:

0.00

AC:

AN:

39026

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064558

Other (OTH)

AF:

0.00

AC:

AN:

58460

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.0017

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.057

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.83

M_CAP

Benign

0.034

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

PhyloP100

1.7

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.19

Sift

Benign

0.19

Sift4G

Benign

0.18

Polyphen

0.030

Vest4

0.34

MutPred

0.42

Loss of ubiquitination at K58 (P = 0.1037)

MVP

0.77

MPC

0.95

ClinPred

0.93

GERP RS

3.5

Varity_R

0.18

gMVP

0.48

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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