Variant 4-165379513-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000402744.9(CPE):c.292G>A(p.Gly98Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CPE
ENST00000402744.9 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.79

Variant links:

Genes affected

CPE (HGNC:2303): (carboxypeptidase E) This gene encodes a member of the M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature peptidase. This peripheral membrane protein cleaves C-terminal amino acid residues and is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. This protein may also function independently of its peptidase activity, as a neurotrophic factor that promotes neuronal survival, and as a sorting receptor that binds to regulated secretory pathway proteins, including prohormones. Mutations in this gene are implicated in type 2 diabetes. [provided by RefSeq, Nov 2015]

CPE links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPE	NM_001873.4 linkuse as main transcript	c.292G>A	p.Gly98Ser	missense_variant	1/9	ENST00000402744.9	NP_001864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPE	ENST00000402744.9 linkuse as main transcript	c.292G>A	p.Gly98Ser	missense_variant	1/9	1	NM_001873.4	ENSP00000386104	P1	P16870-1
CPE	ENST00000513982.5 linkuse as main transcript	c.-30+18202G>A		intron_variant		4		ENSP00000424830
CPE	ENST00000480404.1 linkuse as main transcript	n.228G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1437606

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

711972

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CPE-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2024

The CPE c.292G>A variant is predicted to result in the amino acid substitution p.Gly98Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.094

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.34

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0080

Polyphen

0.95

Vest4

0.51

MVP

0.47

MPC

0.95

ClinPred

0.99

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.70

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