Variant 12-68859062-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198320.5(CPM):c.950G>T(p.Gly317Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000747 in 1,339,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

CPM
NM_198320.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

CPM (HGNC:2311): (carboxypeptidase M) The protein encoded by this gene is a membrane-bound arginine/lysine carboxypeptidase. Its expression is associated with monocyte to macrophage differentiation. This encoded protein contains hydrophobic regions at the amino and carboxy termini and has 6 potential asparagine-linked glycosylation sites. The active site residues of carboxypeptidases A and B are conserved in this protein. Three alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

CPM links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPM	NM_198320.5 linkuse as main transcript	c.950G>T	p.Gly317Val	missense_variant	8/9	ENST00000551568.6	NP_938079.1	P14384

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPM	ENST00000551568.6 linkuse as main transcript	c.950G>T	p.Gly317Val	missense_variant	8/9	1	NM_198320.5	ENSP00000448517.1	P14384
CPM	ENST00000338356.7 linkuse as main transcript	c.950G>T	p.Gly317Val	missense_variant	7/8	1		ENSP00000339157.3	P14384
CPM	ENST00000546373.5 linkuse as main transcript	c.950G>T	p.Gly317Val	missense_variant	8/9	1		ENSP00000447255.1	P14384
CPM	ENST00000551897.5 linkuse as main transcript	c.356G>T	p.Gly119Val	missense_variant	4/6	5		ENSP00000447455.1	H0YHN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.47e-7

AC:

AN:

1339284

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000165

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 01, 2024

The c.950G>T (p.G317V) alteration is located in exon 8 (coding exon 7) of the CPM gene. This alteration results from a G to T substitution at nucleotide position 950, causing the glycine (G) at amino acid position 317 to be replaced by a valine (V). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D;.

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

4.0

H;H;H

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-8.6

D;D;D

REVEL

Pathogenic

0.85

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.97

MutPred

0.73

Gain of catalytic residue at L313 (P = 0.0018);Gain of catalytic residue at L313 (P = 0.0018);Gain of catalytic residue at L313 (P = 0.0018);

MVP

0.92

MPC

1.6

ClinPred

1.0

GERP RS

5.6

Varity_R

0.97

gMVP

0.98

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over