10-123746804-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198148.3(CPXM2):ā€‹c.2231G>Cā€‹(p.Arg744Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000756 in 1,614,228 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00046 ( 0 hom., cov: 32)
Exomes š‘“: 0.00079 ( 2 hom. )

Consequence

CPXM2
NM_198148.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.056640774).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPXM2NM_198148.3 linkuse as main transcriptc.2231G>C p.Arg744Pro missense_variant 14/14 ENST00000241305.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPXM2ENST00000241305.4 linkuse as main transcriptc.2231G>C p.Arg744Pro missense_variant 14/141 NM_198148.3 P1
CPXM2ENST00000615851.4 linkuse as main transcriptc.505+7859G>C intron_variant 5
CPXM2ENST00000368854.7 linkuse as main transcriptn.2064+7859G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000460
AC:
70
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000867
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000609
AC:
153
AN:
251410
Hom.:
0
AF XY:
0.000559
AC XY:
76
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000508
Gnomad NFE exome
AF:
0.00106
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000787
AC:
1150
AN:
1461874
Hom.:
2
Cov.:
35
AF XY:
0.000787
AC XY:
572
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000711
Gnomad4 NFE exome
AF:
0.000948
Gnomad4 OTH exome
AF:
0.000546
GnomAD4 genome
AF:
0.000459
AC:
70
AN:
152354
Hom.:
0
Cov.:
32
AF XY:
0.000443
AC XY:
33
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000867
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000447
Hom.:
0
Bravo
AF:
0.000431
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000814
AC:
7
ExAC
AF:
0.000651
AC:
79
EpiCase
AF:
0.00104
EpiControl
AF:
0.000771

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 GeneticsJun 11, 2021The c.2231G>C (p.R744P) alteration is located in exon 14 (coding exon 14) of the CPXM2 gene. This alteration results from a G to C substitution at nucleotide position 2231, causing the arginine (R) at amino acid position 744 to be replaced by a proline (P). 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
Benign
0.14
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Pathogenic
0.22
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0059
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.65
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.057
T
MetaSVM
Uncertain
0.65
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
0.99
D;D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.020
N
REVEL
Uncertain
0.54
Sift
Benign
0.13
T
Sift4G
Benign
0.16
T
Polyphen
1.0
D
Vest4
0.30
MVP
0.98
MPC
0.28
ClinPred
0.033
T
GERP RS
3.1
Varity_R
0.27
gMVP
0.80

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: rs149753704; hg19: chr10-125506320; API