10-123762004-G-A

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

5
8
6

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]

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
CPXM2NM_198148.3 linkuse as main transcriptc.1645C>T p.Arg549Cys missense_variant 11/14 ENST00000241305.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPXM2ENST00000241305.4 linkuse as main transcriptc.1645C>T p.Arg549Cys missense_variant 11/141 NM_198148.3 P1
CPXM2ENST00000615851.4 linkuse as main transcriptc.133C>T p.Arg45Cys missense_variant 11/155
CPXM2ENST00000368854.7 linkuse as main transcriptn.1692C>T non_coding_transcript_exon_variant 13/202

Frequencies

GnomAD3 genomes
AF:
0.00106
AC:
162
AN:
152158
Hom.:
1
Cov.:
32
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.:
1
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.:
6
Cov.:
31
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.:
1
Cov.:
32
AF XY:
0.00111
AC XY:
83
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.:
0
Bravo
AF:
0.00124
TwinsUK
AF:
0.00243
AC:
9
ALSPAC
AF:
0.00259
AC:
10
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00174
AC:
15
ExAC
AF:
0.000758
AC:
92
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 submitterclinical testingAmbry GeneticsJul 15, 2021The 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
T
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.084
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.7
.;H
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.74
T
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
D
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.

Other links and lift over

dbSNP: rs150707293; hg19: chr10-125521520; API