chr10-123756313-C-T

Position:

• chr10-123756313-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198148.3(CPXM2):​c.1917+900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 152,240 control chromosomes in the GnomAD database, including 200 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 0.046 (200 hom., cov: 34)
• Consequence: CPXM2 NM_198148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPXM2	NM_198148.3	c.1917+900G>A		intron_variant		ENST00000241305.4	NP_937791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPXM2	ENST00000241305.4	c.1917+900G>A		intron_variant		1	NM_198148.3	ENSP00000241305	P1
CPXM2	ENST00000615851.4	c.405+900G>A		intron_variant		5		ENSP00000483180
CPXM2	ENST00000368854.7	n.1964+900G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6959 AN: 152122 Hom.: 201 Cov.: 34

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0565

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

GnomAD4 genome AF: 0.0457 AC: 6958 AN: 152240 Hom.: 200 Cov.: 34 AF XY: 0.0477 AC XY: 3551 AN XY: 74432

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0550 Hom.: 240

Bravo AF: 0.0469

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs1896376; hg19: chr10-125515829;