Variant 20-2794213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019609.5(CPXM1):c.2182C>T(p.Arg728Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CPXM1
NM_019609.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

CPXM1 (HGNC:15771): (carboxypeptidase X, M14 family member 1) This gene likely encodes a member of the carboxypeptidase family of proteins. Cloning of a comparable locus in mouse indicates that the encoded protein contains a discoidin domain and a carboxypeptidase domain, but the protein appears to lack residues necessary for carboxypeptidase activity.[provided by RefSeq, May 2010]

CPXM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.099681705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPXM1	NM_019609.5 linkuse as main transcript	c.2182C>T	p.Arg728Trp	missense_variant	14/14	ENST00000380605.3	NP_062555.1
CPXM1	NM_001184699.2 linkuse as main transcript	c.1960C>T	p.Arg654Trp	missense_variant	14/14		NP_001171628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPXM1	ENST00000380605.3 linkuse as main transcript	c.2182C>T	p.Arg728Trp	missense_variant	14/14	1	NM_019609.5	ENSP00000369979	P1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000802

AC:

AN:

249508

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.000568

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1460900

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000118

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

The c.2182C>T (p.R728W) alteration is located in exon 14 (coding exon 14) of the CPXM1 gene. This alteration results from a C to T substitution at nucleotide position 2182, causing the arginine (R) at amino acid position 728 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

REVEL

Benign

0.22

Sift

Benign

0.040

Sift4G

Uncertain

0.0020

Polyphen

0.0040

Vest4

0.39

MVP

0.95

MPC

0.32

ClinPred

0.043

GERP RS

2.5

Varity_R

0.077

gMVP

0.57

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

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