rs183172032

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016134.4(CPQ):​c.19G>A​(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,597,982 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: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

CPQ
NM_016134.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.248
Variant links:
Genes affected
CPQ (HGNC:16910): (carboxypeptidase Q) This gene encodes a metallopeptidase that belongs to the peptidase M28 family. The encoded protein may catalyze the cleavage of dipeptides with unsubstituted terminals into amino acids. [provided by RefSeq, Jul 2013]

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=0.015446126).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPQNM_016134.4 linkc.19G>A p.Ala7Thr missense_variant Exon 2 of 8 ENST00000220763.10 NP_057218.1 Q9Y646A0A024R9B8
LOC124901985XR_007061019.1 linkn.354+6626C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPQENST00000220763.10 linkc.19G>A p.Ala7Thr missense_variant Exon 2 of 8 1 NM_016134.4 ENSP00000220763.5 Q9Y646

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
151980
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000167
AC:
4
AN:
239220
Hom.:
0
AF XY:
0.0000231
AC XY:
3
AN XY:
129818
show subpopulations
Gnomad AFR exome
AF:
0.000253
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000284
AC:
41
AN:
1445884
Hom.:
0
Cov.:
31
AF XY:
0.0000223
AC XY:
16
AN XY:
718628
show subpopulations
Gnomad4 AFR exome
AF:
0.000249
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:
0.0000290
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000387
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
2.7
DANN
Benign
0.67
DEOGEN2
Benign
0.0033
T;T;T;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0016
N
LIST_S2
Benign
0.47
T;T;T;T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.015
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.8
N;.;.;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.58
N;N;N;N;N
REVEL
Benign
0.041
Sift
Benign
0.39
T;T;T;T;T
Sift4G
Benign
0.37
T;T;T;T;T
Polyphen
0.0010
B;.;.;.;.
Vest4
0.13
MVP
0.061
MPC
0.11
ClinPred
0.016
T
GERP RS
-5.4
Varity_R
0.027
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183172032; hg19: chr8-97797144; COSMIC: COSV55152812; API