rs138679076

Variant names:

• chr10-123754693-C-G
• NM_198148.3:c.1987G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-123754693-C-G
• chr10-123754693-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198148.3(CPXM2):​c.1987G>C​(p.Val663Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CPXM2 NM_198148.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPXM2	NM_198148.3	c.1987G>C	p.Val663Leu	missense_variant	Exon 13 of 14	ENST00000241305.4	NP_937791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPXM2	ENST00000241305.4	c.1987G>C	p.Val663Leu	missense_variant	Exon 13 of 14	1	NM_198148.3	ENSP00000241305.3
CPXM2	ENST00000615851.4	c.475G>C	p.Val159Leu	missense_variant	Exon 13 of 15	5		ENSP00000483180.1
CPXM2	ENST00000368854.7	n.2034G>C		non_coding_transcript_exon_variant	Exon 15 of 20	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454136 Hom.: 0 Cov.: 27 AF XY: 0.00000691 AC XY: 5 AN XY: 723952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000453

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.011	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	.;D
Vest4		0.81
MutPred		0.79		.;Loss of sheet (P = 0.1398);
MVP		0.58
MPC		0.48
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.34
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-125514209;