chr12-68871919-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_198320.5(CPM):āc.296A>Gā(p.Tyr99Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00025 ( 0 hom., cov: 32)
Exomes š: 0.00025 ( 0 hom. )
Consequence
CPM
NM_198320.5 missense
NM_198320.5 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 3.43
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
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=0.020018756).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPM | NM_198320.5 | c.296A>G | p.Tyr99Cys | missense_variant | 4/9 | ENST00000551568.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPM | ENST00000551568.6 | c.296A>G | p.Tyr99Cys | missense_variant | 4/9 | 1 | NM_198320.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152066Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
38
AN:
152066
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000350 AC: 88AN: 251352Hom.: 0 AF XY: 0.000353 AC XY: 48AN XY: 135838
GnomAD3 exomes
AF:
AC:
88
AN:
251352
Hom.:
AF XY:
AC XY:
48
AN XY:
135838
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000254 AC: 372AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.000257 AC XY: 187AN XY: 727246
GnomAD4 exome
AF:
AC:
372
AN:
1461890
Hom.:
Cov.:
33
AF XY:
AC XY:
187
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000250 AC: 38AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74394
GnomAD4 genome
AF:
AC:
38
AN:
152184
Hom.:
Cov.:
32
AF XY:
AC XY:
19
AN XY:
74394
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
4
ExAC
AF:
AC:
37
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2021 | The c.296A>G (p.Y99C) 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 296, causing the tyrosine (Y) at amino acid position 99 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;.;.
Polyphen
D;D;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at