12-68871895-T-C

Position:

• chr12-68871895-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198320.5(CPM):​c.320A>G​(p.Asp107Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CPM NM_198320.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPM	NM_198320.5	c.320A>G	p.Asp107Gly	missense_variant	4/9	ENST00000551568.6	NP_938079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6	c.320A>G	p.Asp107Gly	missense_variant	4/9	1	NM_198320.5	ENSP00000448517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 11, 2024

The c.320A>G (p.D107G) alteration is located in exon 4 (coding exon 3) of the CPM gene. This alteration results from a A to G substitution at nucleotide position 320, causing the aspartic acid (D) at amino acid position 107 to be replaced by a glycine (G). 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	0.34
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	.;T;.;T;T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.2	D;D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.15	T;T;T;D;T
Sift4G	Uncertain	0.016	D;D;D;.;.
Polyphen		0.94	P;P;P;.;.
Vest4		0.53
MutPred		0.67		Gain of catalytic residue at D107 (P = 9e-04);Gain of catalytic residue at D107 (P = 9e-04);Gain of catalytic residue at D107 (P = 9e-04);Gain of catalytic residue at D107 (P = 9e-04);Gain of catalytic residue at D107 (P = 9e-04);
MVP		0.51
MPC		1.5
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.92
gMVP		0.89

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.

Other links and lift over

hg19: chr12-69265675;