Variant 8-96835000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016134.4(CPQ):c.461C>T(p.Thr154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

CPQ
NM_016134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

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]

CPQ links:

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=0.02039665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPQ	NM_016134.4 linkuse as main transcript	c.461C>T	p.Thr154Ile	missense_variant	3/8	ENST00000220763.10	NP_057218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPQ	ENST00000220763.10 linkuse as main transcript	c.461C>T	p.Thr154Ile	missense_variant	3/8	1	NM_016134.4	ENSP00000220763	P1
CPQ	ENST00000517742.1 linkuse as main transcript	c.461C>T	p.Thr154Ile	missense_variant	4/4	5		ENSP00000429146

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000192

AC:

AN:

250110

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00369

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461038

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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

Feb 15, 2023

The c.461C>T (p.T154I) 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 461, causing the threonine (T) at amino acid position 154 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.12

Sift

Benign

0.14

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.11

B;.

Vest4

0.45

MVP

0.44

MPC

0.17

ClinPred

0.10

GERP RS

3.9

Varity_R

0.11

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over