12-68856483-C-T

Variant names:

• chr12-68856483-C-T
• rs150803446
• NM_198320.5:c.1286G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198320.5(CPM):​c.1286G>A​(p.Ser429Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S429T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPM NM_198320.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05021569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198320.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPM	NM_198320.5	MANE Select	c.1286G>A	p.Ser429Asn	missense	Exon 9 of 9	NP_938079.1	P14384
	CPM	NM_001413387.1		c.1322G>A	p.Ser441Asn	missense	Exon 9 of 9	NP_001400316.1
	CPM	NM_001005502.3		c.1286G>A	p.Ser429Asn	missense	Exon 9 of 9	NP_001005502.1	P14384

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPM	ENST00000551568.6	TSL:1 MANE Select	c.1286G>A	p.Ser429Asn	missense	Exon 9 of 9	ENSP00000448517.1	P14384
	CPM	ENST00000338356.7	TSL:1	c.1286G>A	p.Ser429Asn	missense	Exon 8 of 8	ENSP00000339157.3	P14384
	CPM	ENST00000546373.5	TSL:1	c.1286G>A	p.Ser429Asn	missense	Exon 9 of 9	ENSP00000447255.1	P14384

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.74
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.037
Sift	Benign	0.20	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.26		Gain of catalytic residue at K427 (P = 0)
MVP		0.16
MPC		0.53
ClinPred		0.074	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.55
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs150803446; hg19: chr12-69250263;