rs9060

Positions:

• chr10-123745937-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.*827G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,622 control chromosomes in the GnomAD database, including 10,133 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 0.35 (10133 hom., cov: 31)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: CPXM2 NM_198148.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPXM2	NM_198148.3	c.*827G>A		3_prime_UTR_variant	14/14	ENST00000241305.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPXM2	ENST00000241305.4	c.*827G>A		3_prime_UTR_variant	14/14	1	NM_198148.3	P1
CPXM2	ENST00000615851.4	c.505+8726G>A		intron_variant		5
CPXM2	ENST00000368854.7	n.2064+8726G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52543 AN: 151474 Hom.: 10116 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.267 AC: 8 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 6 AN XY: 24

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.269

GnomAD4 genome AF: 0.347 AC: 52603 AN: 151592 Hom.: 10133 Cov.: 31 AF XY: 0.342 AC XY: 25366 AN XY: 74076

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.0620

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.345

Alfa AF: 0.309 Hom.: 7289

Bravo AF: 0.353

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.28

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: rs9060; hg19: chr10-125505453;