10-123761877-G-A

Variant names:

• chr10-123761877-G-A
• NM_198148.3:c.1772C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198148.3(CPXM2):​c.1772C>T​(p.Ala591Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPXM2 NM_198148.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.98
• Publications: 0 publications found

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]

ENSG00000231138 (HGNC:58377):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPXM2	NM_198148.3	c.1772C>T	p.Ala591Val	missense_variant	Exon 11 of 14	ENST00000241305.4	NP_937791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPXM2	ENST00000241305.4	c.1772C>T	p.Ala591Val	missense_variant	Exon 11 of 14	1	NM_198148.3	ENSP00000241305.3
CPXM2	ENST00000615851.4	c.260C>T	p.Ala87Val	missense_variant	Exon 11 of 15	5		ENSP00000483180.1
CPXM2	ENST00000368854.7	n.1819C>T		non_coding_transcript_exon_variant	Exon 13 of 20	2
ENSG00000231138	ENST00000818156.1	n.142+591G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1772C>T (p.A591V) 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 1772, causing the alanine (A) at amino acid position 591 to be replaced by a valine (V). 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	0.25
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L
PhyloP100		10
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.0	.;N
REVEL	Benign	0.23
Sift	Benign	0.13	.;T
Sift4G	Benign	0.23	T;T
Polyphen		0.053	.;B
Vest4		0.68
MutPred		0.60		.;Loss of sheet (P = 0.1158);
MVP		0.59
MPC		0.33
ClinPred		0.76	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.60
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

hg19: chr10-125521393;