10-123761919-T-C

Variant names:

• chr10-123761919-T-C
• rs112981683
• NM_198148.3:c.1730A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198148.3(CPXM2):​c.1730A>G​(p.Lys577Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00289 in 1,613,896 control chromosomes in the GnomAD database, including 108 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: CPXM2 NM_198148.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.16
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003206253).
• BP6: Variant 10-123761919-T-C is Benign according to our data. Variant chr10-123761919-T-C is described in ClinVar as Benign. ClinVar VariationId is 768399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198148.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPXM2	NM_198148.3	MANE Select	c.1730A>G	p.Lys577Arg	missense	Exon 11 of 14	NP_937791.2	Q8N436

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPXM2	ENST00000241305.4	TSL:1 MANE Select	c.1730A>G	p.Lys577Arg	missense	Exon 11 of 14	ENSP00000241305.3	Q8N436
	CPXM2	ENST00000909350.1		c.1727A>G	p.Lys576Arg	missense	Exon 11 of 14	ENSP00000579409.1
	CPXM2	ENST00000909348.1		c.1631A>G	p.Lys544Arg	missense	Exon 10 of 13	ENSP00000579407.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2287 AN: 152130 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00403 AC: 1009 AN: 250332 AF XY: 0.00294

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00163 AC: 2382 AN: 1461648 Hom.: 52 Cov.: 31 AF XY: 0.00148 AC XY: 1076 AN XY: 727120

African (AFR) AF: 0.0573 AC: 1919 AN: 33474

American (AMR) AF: 0.00246 AC: 110 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00573 AC: 33 AN: 5764

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111900

Other (OTH) AF: 0.00383 AC: 231 AN: 60386

GnomAD4 genome AF: 0.0150 AC: 2290 AN: 152248 Hom.: 56 Cov.: 32 AF XY: 0.0151 AC XY: 1121 AN XY: 74460

African (AFR) AF: 0.0519 AC: 2156 AN: 41544

American (AMR) AF: 0.00588 AC: 90 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68010

Other (OTH) AF: 0.0128 AC: 27 AN: 2108

Alfa AF: 0.00543 Hom.: 37

Bravo AF: 0.0173

ESP6500AA AF: 0.0574 AC: 253

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00496 AC: 602

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0054	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.64	N
PhyloP100		6.2
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.17
Sift	Benign	0.49	T
Sift4G	Benign	0.57	T
Polyphen		0.76	P
Vest4		0.59
MVP		0.49
MPC		0.17
ClinPred		0.041	T
GERP RS		5.4
Varity_R		0.23
gMVP		0.54
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112981683; hg19: chr10-125521435;