rs1006581715

Variant names:

• chr12-68869343-A-C
• rs1006581715
• NM_198320.5:c.769T>G

Your query was ambiguous. Multiple possible variants found:

• chr12-68869343-A-C
• chr12-68869343-A-G
• chr12-68869343-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198320.5(CPM):​c.769T>G​(p.Ser257Ala) 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. 15/21 in silico tools predict a benign 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: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05763161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPM	NM_198320.5	c.769T>G	p.Ser257Ala	missense_variant	Exon 6 of 9	ENST00000551568.6	NP_938079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6	c.769T>G	p.Ser257Ala	missense_variant	Exon 6 of 9	1	NM_198320.5	ENSP00000448517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.75
DEOGEN2	Benign	0.0085	T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.37	.;T;.
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.50	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.16	N;N;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.14
MutPred		0.52		Gain of catalytic residue at S257 (P = 0);Gain of catalytic residue at S257 (P = 0);Gain of catalytic residue at S257 (P = 0);
MVP		0.10
MPC		0.41
ClinPred		0.027	T
GERP RS		-0.20
Varity_R		0.12
gMVP		0.47

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

Other links and lift over

dbSNP: rs1006581715; hg19: chr12-69263123; COSMIC: COSV105239124; COSMIC: COSV105239124;