NM_019609.5:c.1693G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_019609.5(CPXM1):​c.1693G>C​(p.Gly565Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CPXM1
NM_019609.5 missense

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
CPXM1 (HGNC:15771): (carboxypeptidase X, M14 family member 1) This gene likely encodes a member of the carboxypeptidase family of proteins. Cloning of a comparable locus in mouse indicates that the encoded protein contains a discoidin domain and a carboxypeptidase domain, but the protein appears to lack residues necessary for carboxypeptidase activity.[provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPXM1NM_019609.5 linkc.1693G>C p.Gly565Arg missense_variant Exon 11 of 14 ENST00000380605.3 NP_062555.1 Q96SM3
CPXM1NM_001184699.2 linkc.1498+195G>C intron_variant Intron 11 of 13 NP_001171628.1 Q96SM3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPXM1ENST00000380605.3 linkc.1693G>C p.Gly565Arg missense_variant Exon 11 of 14 1 NM_019609.5 ENSP00000369979.2 Q96SM3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1693G>C (p.G565R) alteration is located in exon 11 (coding exon 11) of the CPXM1 gene. This alteration results from a G to C substitution at nucleotide position 1693, causing the glycine (G) at amino acid position 565 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.29
T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.017
T
MetaRNN
Pathogenic
0.94
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Uncertain
0.46
Sift
Benign
0.046
D
Sift4G
Benign
0.097
T
Polyphen
1.0
D
Vest4
0.99
MutPred
0.79
Gain of catalytic residue at G565 (P = 0.012);
MVP
0.65
MPC
1.1
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.63
gMVP
0.98

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: chr20-2776272; API