Variant 10-123754772-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198148.3(CPXM2):c.1918-10T>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009937

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.680

Variant links:

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]

CPXM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CPXM2	NM_198148.3 linkuse as main transcript	c.1918-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000241305.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CPXM2	ENST00000241305.4 linkuse as main transcript	c.1918-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_198148.3	P1
CPXM2	ENST00000615851.4 linkuse as main transcript	c.406-10T>C	splice_polypyrimidine_tract_variant, intron_variant	5
CPXM2	ENST00000368854.7 linkuse as main transcript	n.1965-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3390

AN:

152194

Hom.:

120

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00604

AC:

1519

AN:

251316

Hom.:

AF XY:

0.00452

AC XY:

614

AN XY:

135816

show subpopulations

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 SAS exome

AF:

0.00137

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.:

AF XY:

0.00214

AC XY:

1484

AN XY:

693766

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.00377

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.00633

GnomAD4 genome

AF:

0.0224

AC:

3405

AN:

152312

Hom.:

122

Cov.:

AF XY:

0.0216

AC XY:

1612

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0783

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00843

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

DANN

Benign

0.40

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over