Variant 3-194341594-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080513.4(CPN2):c.1109A>G(p.Lys370Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CPN2
NM_001080513.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

Variant links:

Genes affected

CPN2 (HGNC:2313): (carboxypeptidase N subunit 2) Predicted to be involved in regulation of catalytic activity. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CPN2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0658313).

BP6

Variant 3-194341594-T-C is Benign according to our data. Variant chr3-194341594-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3076733.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CPN2	NM_001080513.4 linkuse as main transcript	c.1109A>G	p.Lys370Arg	missense_variant	2/2	ENST00000323830.4	NP_001073982.3
CPN2	NM_001291988.2 linkuse as main transcript	c.1109A>G	p.Lys370Arg	missense_variant	2/2		NP_001278917.1
CPN2	XM_005269280.5 linkuse as main transcript	c.1109A>G	p.Lys370Arg	missense_variant	3/3		XP_005269337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPN2	ENST00000323830.4 linkuse as main transcript	c.1109A>G	p.Lys370Arg	missense_variant	2/2	1	NM_001080513.4	ENSP00000319464	P1
CPN2	ENST00000429275.1 linkuse as main transcript	c.1109A>G	p.Lys370Arg	missense_variant	2/2	5		ENSP00000402232	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

DANN

Benign

0.26

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.41

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.017

MutPred

0.42

Loss of ubiquitination at K370 (P = 0.0098);Loss of ubiquitination at K370 (P = 0.0098);

MVP

0.34

MPC

0.15

ClinPred

0.022

GERP RS

-0.022

Varity_R

0.057

gMVP

0.35

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