chr10-123754752-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_198148.3(CPXM2):​c.1928G>A​(p.Gly643Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,593,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

CPXM2
NM_198148.3 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPXM2NM_198148.3 linkuse as main transcriptc.1928G>A p.Gly643Asp missense_variant 13/14 ENST00000241305.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPXM2ENST00000241305.4 linkuse as main transcriptc.1928G>A p.Gly643Asp missense_variant 13/141 NM_198148.3 P1
CPXM2ENST00000615851.4 linkuse as main transcriptc.416G>A p.Gly139Asp missense_variant 13/155
CPXM2ENST00000368854.7 linkuse as main transcriptn.1975G>A non_coding_transcript_exon_variant 15/202

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000119
AC:
30
AN:
251446
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000694
AC:
100
AN:
1440872
Hom.:
0
Cov.:
26
AF XY:
0.0000682
AC XY:
49
AN XY:
718376
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00192
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000201
Gnomad4 OTH exome
AF:
0.000235
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000261
Hom.:
0
Bravo
AF:
0.0000869
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 GeneticsFeb 16, 2023The c.1928G>A (p.G643D) alteration is located in exon 13 (coding exon 13) of the CPXM2 gene. This alteration results from a G to A substitution at nucleotide position 1928, causing the glycine (G) at amino acid position 643 to be replaced by an aspartic acid (D). 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
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;D
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Benign
0.084
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Pathogenic
3.9
.;H
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-6.4
.;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
.;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
.;D
Vest4
0.98
MutPred
0.85
.;Loss of MoRF binding (P = 0.0399);
MVP
0.67
MPC
0.87
ClinPred
0.99
D
GERP RS
4.3
Varity_R
0.92
gMVP
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs138945308; hg19: chr10-125514268; API