10-123771393-G-C

Variant names:

• chr10-123771393-G-C
• rs727417
• NM_198148.3:c.979-354C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198148.3(CPXM2):​c.979-354C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,140 control chromosomes in the GnomAD database, including 65,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (65260 hom., cov: 30)
• Consequence: CPXM2 NM_198148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.938 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.979-354C>G		intron	N/A	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.979-354C>G		intron	N/A	ENSP00000241305.3	Q8N436
	CPXM2	ENST00000909350.1		c.976-354C>G		intron	N/A	ENSP00000579409.1
	CPXM2	ENST00000909348.1		c.880-354C>G		intron	N/A	ENSP00000579407.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140778 AN: 152022 Hom.: 65214 Cov.: 30

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.926 AC: 140883 AN: 152140 Hom.: 65260 Cov.: 30 AF XY: 0.924 AC XY: 68722 AN XY: 74356

African (AFR) AF: 0.900 AC: 37358 AN: 41504

American (AMR) AF: 0.903 AC: 13799 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3275 AN: 3472

East Asian (EAS) AF: 0.931 AC: 4798 AN: 5154

South Asian (SAS) AF: 0.888 AC: 4271 AN: 4810

European-Finnish (FIN) AF: 0.949 AC: 10051 AN: 10590

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64209 AN: 68010

Other (OTH) AF: 0.925 AC: 1951 AN: 2110

Alfa AF: 0.936 Hom.: 8268

Bravo AF: 0.919

Asia WGS AF: 0.921 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs727417; hg19: chr10-125530909;