rs570491377

Variant names:

• chr12-68856535-T-A
• NM_198320.5:c.1234A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-68856535-T-A
• chr12-68856535-T-C

Variant summary

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

The NM_198320.5(CPM):​c.1234A>T​(p.Met412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPM NM_198320.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

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=0.042914003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPM	NM_198320.5	c.1234A>T	p.Met412Leu	missense_variant	Exon 9 of 9	ENST00000551568.6	NP_938079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6	c.1234A>T	p.Met412Leu	missense_variant	Exon 9 of 9	1	NM_198320.5	ENSP00000448517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.69
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.62	.;T;.
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.15
MutPred		0.35		Gain of catalytic residue at C410 (P = 0.0224);Gain of catalytic residue at C410 (P = 0.0224);Gain of catalytic residue at C410 (P = 0.0224);
MVP		0.16
MPC		0.46
ClinPred		0.033	T
GERP RS		-2.2
Varity_R		0.19
gMVP		0.52

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: chr12-69250315;