chr8-96835102-C-T

Variant summary

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

The NM_016134.4(CPQ):​c.563C>T​(p.Thr188Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000575 in 1,601,072 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CPQ
NM_016134.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740
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=0.050864667).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CPQNM_016134.4 linkuse as main transcriptc.563C>T p.Thr188Met missense_variant 3/8 ENST00000220763.10 NP_057218.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CPQENST00000220763.10 linkuse as main transcriptc.563C>T p.Thr188Met missense_variant 3/81 NM_016134.4 ENSP00000220763 P1
CPQENST00000517742.1 linkuse as main transcript downstream_gene_variant 5 ENSP00000429146

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000377
AC:
9
AN:
238714
Hom.:
0
AF XY:
0.0000309
AC XY:
4
AN XY:
129508
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000635
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:
0.0000641
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000600
AC:
87
AN:
1448914
Hom.:
0
Cov.:
29
AF XY:
0.0000527
AC XY:
38
AN XY:
720710
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000697
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:
0.0000724
Gnomad4 OTH exome
AF:
0.0000502
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsApr 15, 2024The c.563C>T (p.T188M) alteration is located in exon 3 (coding exon 2) of the CPQ gene. This alteration results from a C to T substitution at nucleotide position 563, causing the threonine (T) at amino acid position 188 to be replaced by a methionine (M). 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
Benign
0.079
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
5.2
DANN
Benign
0.86
DEOGEN2
Benign
0.0054
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.016
N
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.0050
Sift
Benign
0.15
T
Sift4G
Benign
0.28
T
Polyphen
0.019
B
Vest4
0.12
MVP
0.19
MPC
0.13
ClinPred
0.024
T
GERP RS
-1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.017
gMVP
0.58

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

LitVar

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

Other links and lift over

dbSNP: rs757303134; hg19: chr8-97847330; COSMIC: COSV55137584; COSMIC: COSV55137584; API