10-123754772-A-G

Variant names:

• chr10-123754772-A-G
• rs17105929
• NM_198148.3:c.1918-10T>C

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.1918-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,537,406 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (105 hom.)
• Consequence: CPXM2 NM_198148.3 intron
• Scores: Splicing: ADA: 0.00009937
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.680
• 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-123754772-A-G is Benign according to our data. Variant chr10-123754772-A-G is described in ClinVar as [Benign]. Clinvar id is 776549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPXM2	NM_198148.3	c.1918-10T>C		intron_variant	Intron 12 of 13	ENST00000241305.4	NP_937791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPXM2	ENST00000241305.4	c.1918-10T>C		intron_variant	Intron 12 of 13	1	NM_198148.3	ENSP00000241305.3
CPXM2	ENST00000615851.4	c.406-10T>C		intron_variant	Intron 12 of 14	5		ENSP00000483180.1
CPXM2	ENST00000368854.7	n.1965-10T>C		intron_variant	Intron 14 of 19	2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3390 AN: 152194 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00604 AC: 1519 AN: 251316 AF XY: 0.00452

Gnomad AFR exome AF: 0.0812

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00248 AC: 3439 AN: 1385094 Hom.: 105 Cov.: 23 AF XY: 0.00214 AC XY: 1484 AN XY: 693766

African (AFR) AF: 0.0808 AC: 2586 AN: 31994

American (AMR) AF: 0.00377 AC: 168 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.0000390 AC: 1 AN: 25664

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39334

South Asian (SAS) AF: 0.00130 AC: 110 AN: 84750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00515 AC: 29 AN: 5628

European-Non Finnish (NFE) AF: 0.000171 AC: 178 AN: 1041854

Other (OTH) AF: 0.00633 AC: 366 AN: 57864

GnomAD4 genome AF: 0.0224 AC: 3405 AN: 152312 Hom.: 122 Cov.: 33 AF XY: 0.0216 AC XY: 1612 AN XY: 74472

African (AFR) AF: 0.0783 AC: 3253 AN: 41558

American (AMR) AF: 0.00679 AC: 104 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68030

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.0104 Hom.: 81

Bravo AF: 0.0252

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000099
SpliceAI score (max)		0.020		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: rs17105929; hg19: chr10-125514288;