chr10-123746771-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198148.3(CPXM2):​c.2264G>A​(p.Arg755His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

CPXM2
NM_198148.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.622
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08398613).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPXM2NM_198148.3 linkuse as main transcriptc.2264G>A p.Arg755His missense_variant 14/14 ENST00000241305.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPXM2ENST00000241305.4 linkuse as main transcriptc.2264G>A p.Arg755His missense_variant 14/141 NM_198148.3 P1
CPXM2ENST00000615851.4 linkuse as main transcriptc.505+7892G>A intron_variant 5
CPXM2ENST00000368854.7 linkuse as main transcriptn.2064+7892G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000876
AC:
22
AN:
251214
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000725
AC:
106
AN:
1461748
Hom.:
0
Cov.:
29
AF XY:
0.0000963
AC XY:
70
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000499
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000495
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.0000545
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 GeneticsJun 30, 2023The c.2264G>A (p.R755H) alteration is located in exon 14 (coding exon 14) of the CPXM2 gene. This alteration results from a G to A substitution at nucleotide position 2264, causing the arginine (R) at amino acid position 755 to be replaced by a histidine (H). 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
0.097
BayesDel_addAF
Benign
-0.098
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.30
T
M_CAP
Pathogenic
0.45
D
MetaRNN
Benign
0.084
T
MetaSVM
Uncertain
0.25
D
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.78
D;D
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.59
N
REVEL
Uncertain
0.29
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.013
B
Vest4
0.22
MVP
0.78
MPC
0.24
ClinPred
0.069
T
GERP RS
3.5
Varity_R
0.092
gMVP
0.57

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: rs750948954; hg19: chr10-125506287; COSMIC: COSV53860220; API