Variant chr2-37352828-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000338415.8(QPCT):c.160C>T(p.Arg54Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,613,994 control chromosomes in the GnomAD database, including 6,557 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.061 ( 839 hom., cov: 32)

Exomes 𝑓: 0.034 ( 5718 hom. )

Consequence

QPCT
ENST00000338415.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016189218).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QPCT	NM_012413.4 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	2/7	ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8 linkuse as main transcript	c.160C>T	p.Arg54Trp	missense_variant	2/7	1	NM_012413.4	ENSP00000344829	P1	Q16769-1
QPCT	ENST00000650442.1 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant	2/4			ENSP00000498156
QPCT	ENST00000404976.5 linkuse as main transcript	c.121-6752C>T		intron_variant		2		ENSP00000385391
QPCT	ENST00000470075.1 linkuse as main transcript	n.164C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9215

AN:

152108

Hom.:

844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.0734

Gnomad FIN

AF:

0.0804

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00888

Gnomad OTH

AF:

0.0637

GnomAD3 exomes

AF:

0.0970

AC:

24392

AN:

251434

Hom.:

3619

AF XY:

0.0841

AC XY:

11434

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.0643

Gnomad FIN exome

AF:

0.0763

Gnomad NFE exome

AF:

0.00868

Gnomad OTH exome

AF:

0.0686

GnomAD4 exome

AF:

0.0336

AC:

49043

AN:

1461768

Hom.:

5718

Cov.:

AF XY:

0.0329

AC XY:

23944

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0594

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.00738

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.0619

Gnomad4 FIN exome

AF:

0.0774

Gnomad4 NFE exome

AF:

0.00591

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0607

AC:

9237

AN:

152226

Hom.:

839

Cov.:

AF XY:

0.0685

AC XY:

5097

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0601

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.0732

Gnomad4 FIN

AF:

0.0804

Gnomad4 NFE

AF:

0.00888

Gnomad4 OTH

AF:

0.0668

Alfa

AF:

0.0298

Hom.:

1198

Bravo

AF:

0.0747

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.0552

AC:

243

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.0842

AC:

10224

Asia WGS

AF:

0.184

AC:

637

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Benign

0.14

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.086

MPC

0.018

ClinPred

0.032

GERP RS

4.8

Varity_R

0.29

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over