Genetic Variant NM_153634.3:c.187T>C (chr12-38848662-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153634.3(CPNE8):c.187T>C(p.Phe63Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CPNE8
NM_153634.3 missense, splice_region

Scores

Splicing: ADA: 0.007118

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.99

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.187T>C	p.Phe63Leu	missense splice_region	Exon 4 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.187T>C	p.Phe63Leu	missense splice_region	Exon 4 of 20	ENSP00000329748.5	Q86YQ8-1
CPNE8	ENST00000360449.3	TSL:2	c.151T>C	p.Phe51Leu	missense splice_region	Exon 4 of 20	ENSP00000353633.3	E7ENV7
CPNE8	ENST00000862791.1		c.187T>C	p.Phe63Leu	missense splice_region	Exon 4 of 20	ENSP00000532850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712664

African (AFR)

AF:

0.00

AC:

AN:

31464

American (AMR)

AF:

0.00

AC:

AN:

37662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25498

East Asian (EAS)

AF:

0.00

AC:

AN:

38622

South Asian (SAS)

AF:

0.00

AC:

AN:

80146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4954

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103182

Other (OTH)

AF:

0.00

AC:

AN:

59174

GnomAD4 genome

Cov.:

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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.0019

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.056

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

PhyloP100

9.0

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.28

Sift

Benign

0.46

Sift4G

Benign

0.66

Polyphen

0.0070

Vest4

0.79

MutPred

0.35

Loss of sheet (P = 0.0817)

MVP

0.40

MPC

0.86

ClinPred

0.98

GERP RS

3.6

Varity_R

0.30

gMVP

0.28

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0071

dbscSNV1_RF

Benign

0.040

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