dbSNP rs1250710190: CPNE5:p.Gly411Ser (chr6-36745485-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_020939.2(CPNE5):c.1231G>A(p.Gly411Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,600,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CPNE5
NM_020939.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

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.1231G>A	p.Gly411Ser	missense	Exon 17 of 21	NP_065990.1	Q9HCH3-1
CPNE5	NM_001410887.1		c.1282G>A	p.Gly428Ser	missense	Exon 18 of 22	NP_001397816.1	A0A0J9YWA1
CPNE5	NM_001376889.1		c.1282G>A	p.Gly428Ser	missense	Exon 18 of 22	NP_001363818.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1231G>A	p.Gly411Ser	missense	Exon 17 of 21	ENSP00000244751.2	Q9HCH3-1
CPNE5	ENST00000393189.2	TSL:1	c.355G>A	p.Gly119Ser	missense	Exon 6 of 10	ENSP00000376885.2	Q9HCH3-2
CPNE5	ENST00000493411.2	TSL:1	n.411G>A		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000224

AC:

AN:

223614

AF XY:

0.0000166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000498

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000195

AC:

282

AN:

1448404

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

128

AN XY:

719120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33324

American (AMR)

AF:

0.00

AC:

AN:

42418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25766

East Asian (EAS)

AF:

0.00

AC:

AN:

39146

South Asian (SAS)

AF:

0.00

AC:

AN:

83656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000252

AC:

279

AN:

1106184

Other (OTH)

AF:

0.0000501

AC:

AN:

59870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000567

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

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.069

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.5

PhyloP100

7.6

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.58

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0010

Polyphen

0.97

Vest4

0.95

MutPred

0.69

Gain of disorder (P = 0.1127)

MVP

0.77

MPC

1.7

ClinPred

0.97

GERP RS

5.0

Varity_R

0.70

gMVP

0.91

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over