chr10-123746792-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198148.3(CPXM2):​c.2243G>A​(p.Arg748Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CPXM2
NM_198148.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011779636).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPXM2NM_198148.3 linkuse as main transcriptc.2243G>A p.Arg748Gln missense_variant 14/14 ENST00000241305.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPXM2ENST00000241305.4 linkuse as main transcriptc.2243G>A p.Arg748Gln missense_variant 14/141 NM_198148.3 P1
CPXM2ENST00000615851.4 linkuse as main transcriptc.505+7871G>A intron_variant 5
CPXM2ENST00000368854.7 linkuse as main transcriptn.2064+7871G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152224
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000195
AC:
49
AN:
251286
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000925
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.0000602
AC:
88
AN:
1461876
Hom.:
0
Cov.:
34
AF XY:
0.0000619
AC XY:
45
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000648
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.000272
AC:
33
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

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 GeneticsSep 16, 2021The c.2243G>A (p.R748Q) 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 2243, causing the arginine (R) at amino acid position 748 to be replaced by a glutamine (Q). 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
0.099
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.012
T
MetaSVM
Uncertain
0.060
D
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.7
N
REVEL
Uncertain
0.32
Sift
Benign
0.23
T
Sift4G
Benign
0.11
T
Polyphen
0.0020
B
Vest4
0.12
MutPred
0.20
Loss of methylation at R752 (P = 0.0496);
MVP
0.76
MPC
0.22
ClinPred
0.018
T
GERP RS
2.4
Varity_R
0.062
gMVP
0.62

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: rs374183184; hg19: chr10-125506308; COSMIC: COSV105015982; API