Variant 3-131535259-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130808.3(CPNE4):c.1610G>A(p.Gly537Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CPNE4
NM_130808.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

CPNE4 (HGNC:2317): (copine 4) This gene belongs to the highly conserved copine family. It encodes a calcium-dependent, phospholipid-binding protein, which may be involved in membrane trafficking, mitogenesis and development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CPNE4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17034718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPNE4	NM_130808.3 linkuse as main transcript	c.1610G>A	p.Gly537Asp	missense_variant	16/16	ENST00000429747.6	NP_570720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPNE4	ENST00000429747.6 linkuse as main transcript	c.1610G>A	p.Gly537Asp	missense_variant	16/16	1	NM_130808.3	ENSP00000411904	P1	Q96A23-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 15, 2021

The c.1610G>A (p.G537D) alteration is located in exon 16 (coding exon 15) of the CPNE4 gene. This alteration results from a G to A substitution at nucleotide position 1610, causing the glycine (G) at amino acid position 537 to be replaced by an aspartic acid (D). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.020

T;.;T;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

D;D;.;.;.;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.26

N;.;N;.;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.080

N;.;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.33

T;.;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T;T

Polyphen

0.046

B;B;B;B;B;B

Vest4

0.31

MutPred

0.35

Gain of glycosylation at Y534 (P = 0.0101);.;Gain of glycosylation at Y534 (P = 0.0101);.;Gain of glycosylation at Y534 (P = 0.0101);.;

MVP

0.21

MPC

1.3

ClinPred

0.54

GERP RS

5.3

Varity_R

0.31

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over