Variant chr2-37367374-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012413.4(QPCT):c.689C>G(p.Pro230Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

QPCT
NM_012413.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

QPCT (HGNC:9753): (glutaminyl-peptide cyclotransferase) This gene encodes human pituitary glutaminyl cyclase, which is responsible for the presence of pyroglutamyl residues in many neuroendocrine peptides. The amino acid sequence of this enzyme is 86% identical to that of bovine glutaminyl cyclase. [provided by RefSeq, Jul 2008]

QPCT links:

QPCT (HGNC:):

QPCT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPCT	NM_012413.4 linkuse as main transcript	c.689C>G	p.Pro230Arg	missense_variant	4/7	ENST00000338415.8	NP_036545.1	Q16769-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QPCT	ENST00000338415.8 linkuse as main transcript	c.689C>G	p.Pro230Arg	missense_variant	4/7	1	NM_012413.4	ENSP00000344829.3	Q16769-1
QPCT	ENST00000404976.5 linkuse as main transcript	c.542C>G	p.Pro181Arg	missense_variant	3/6	2		ENSP00000385391.1	B5MCZ9
QPCT	ENST00000469098.1 linkuse as main transcript	n.252C>G		non_coding_transcript_exon_variant	1/4	2
QPCT	ENST00000480050.1 linkuse as main transcript	n.599C>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250532

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000885

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 01, 2024

The c.689C>G (p.P230R) alteration is located in exon 4 (coding exon 4) of the QPCT gene. This alteration results from a C to G substitution at nucleotide position 689, causing the proline (P) at amino acid position 230 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

Benign

0.090

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;T

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.50

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.22

Sift

Benign

0.035

D;D

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.61

MutPred

0.49

Loss of glycosylation at P230 (P = 0.0113);.;

MVP

0.41

MPC

0.12

ClinPred

0.99

GERP RS

5.5

Varity_R

0.59

gMVP

0.64

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