Variant chr10-123762004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198148.3(CPXM2):c.1645C>T(p.Arg549Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00166 in 1,613,720 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

CPXM2
NM_198148.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

CPXM2 (HGNC:26977): (carboxypeptidase X, M14 family member 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in peptide metabolic process and protein processing. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CPXM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08376396).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPXM2	NM_198148.3 linkuse as main transcript	c.1645C>T	p.Arg549Cys	missense_variant	11/14	ENST00000241305.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CPXM2	ENST00000241305.4 linkuse as main transcript	c.1645C>T	p.Arg549Cys	missense_variant	11/14	1	NM_198148.3	P1
CPXM2	ENST00000615851.4 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	11/15	5
CPXM2	ENST00000368854.7 linkuse as main transcript	n.1692C>T		non_coding_transcript_exon_variant	13/20	2

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

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:

0.00160

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000849

AC:

213

AN:

250980

Hom.:

AF XY:

0.000840

AC XY:

114

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00173

AC:

2523

AN:

1461444

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1223

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152276

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.00202

EpiControl

AF:

0.00178

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

Jul 15, 2021

The c.1645C>T (p.R549C) alteration is located in exon 11 (coding exon 11) of the CPXM2 gene. This alteration results from a C to T substitution at nucleotide position 1645, causing the arginine (R) at amino acid position 549 to be replaced by a cysteine (C). 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

0.53

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.076

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.7

.;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.8

.;D

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.66

MVP

0.34

MPC

0.87

ClinPred

0.59

GERP RS

4.4

Varity_R

0.77

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over