Genetic Variant CPNE5:p.Arg531Leu (chr6-36742458-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020939.2(CPNE5):c.1592G>T(p.Arg531Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R531H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CPNE5
NM_020939.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10

Publications

1 publications found

Variant links:

Genes affected

CPNE5 (HGNC:2318): (copine 5) 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. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

CPNE5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2717595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020939.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE5	NM_020939.2	MANE Select	c.1592G>T	p.Arg531Leu	missense	Exon 21 of 21	NP_065990.1	Q9HCH3-1
CPNE5	NM_001410887.1		c.1643G>T	p.Arg548Leu	missense	Exon 22 of 22	NP_001397816.1	A0A0J9YWA1
CPNE5	NM_001314018.2		c.716G>T	p.Arg239Leu	missense	Exon 10 of 10	NP_001300947.1	Q9HCH3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1592G>T	p.Arg531Leu	missense	Exon 21 of 21	ENSP00000244751.2	Q9HCH3-1
CPNE5	ENST00000393189.2	TSL:1	c.716G>T	p.Arg239Leu	missense	Exon 10 of 10	ENSP00000376885.2	Q9HCH3-2
CPNE5	ENST00000493411.2	TSL:1	n.772G>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249782

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726672

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111900

Other (OTH)

AF:

0.00

AC:

AN:

60376

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.037

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

3.1

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.27

Sift

Benign

0.15

Sift4G

Benign

0.20

Polyphen

0.026

Vest4

0.46

MutPred

0.55

Loss of MoRF binding (P = 0.0353)

MVP

0.44

MPC

1.8

ClinPred

0.89

GERP RS

4.9

Varity_R

0.45

gMVP

0.83

Mutation Taster

=31/69

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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