rs1006581715

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198320.5(CPM):​c.769T>A​(p.Ser257Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPM NM_198320.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0330
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08363229).

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.769T>A	p.Ser257Thr	missense	Exon 6 of 9	NP_938079.1	P14384
	CPM	NM_001413387.1		c.805T>A	p.Ser269Thr	missense	Exon 6 of 9	NP_001400316.1
	CPM	NM_001005502.3		c.769T>A	p.Ser257Thr	missense	Exon 6 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.769T>A	p.Ser257Thr	missense	Exon 6 of 9	ENSP00000448517.1	P14384
	CPM	ENST00000338356.7	TSL:1	c.769T>A	p.Ser257Thr	missense	Exon 5 of 8	ENSP00000339157.3	P14384
	CPM	ENST00000546373.5	TSL:1	c.769T>A	p.Ser257Thr	missense	Exon 6 of 9	ENSP00000447255.1	P14384

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460918 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726786

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.0000225 AC: 1 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111500

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.033
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.017
Sift	Benign	0.094	T
Sift4G	Benign	0.49	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.47		Gain of catalytic residue at Q262 (P = 0.001)
MVP		0.14
MPC		0.45
ClinPred		0.055	T
GERP RS		-0.20
Varity_R		0.19
gMVP		0.54
Mutation Taster		=87/13	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: rs1006581715; hg19: chr12-69263123;