Variant 2-37372684-G-A 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.943G>A(p.Val315Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

QPCT
NM_012413.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86

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 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	UniProt
QPCT	NM_012413.4 linkuse as main transcript	c.943G>A	p.Val315Ile	missense_variant, splice_region_variant	7/7	ENST00000338415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QPCT	ENST00000338415.8 linkuse as main transcript	c.943G>A	p.Val315Ile	missense_variant, splice_region_variant	7/7	1	NM_012413.4	P1	Q16769-1
QPCT	ENST00000404976.5 linkuse as main transcript	c.796G>A	p.Val266Ile	missense_variant, splice_region_variant	6/6	2
QPCT	ENST00000444022.1 linkuse as main transcript	c.238G>A	p.Val80Ile	missense_variant, splice_region_variant	4/4	5
QPCT	ENST00000469098.1 linkuse as main transcript	n.506G>A		splice_region_variant, non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249146

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134604

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1459964

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000261

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000501

Hom.:

Bravo

AF:

0.0000189

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

Apr 25, 2023

The c.943G>A (p.V315I) alteration is located in exon 7 (coding exon 7) of the QPCT gene. This alteration results from a G to A substitution at nucleotide position 943, causing the valine (V) at amino acid position 315 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

0.10

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.28

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.085

T;T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.95

N;N;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.024

D;T;D

Sift4G

Uncertain

0.060

T;D;D

Polyphen

0.99

D;.;.

Vest4

0.42

MutPred

0.80

Gain of catalytic residue at L320 (P = 0.0631);.;.;

MVP

0.60

MPC

0.045

ClinPred

0.57

GERP RS

5.9

Varity_R

0.40

gMVP

0.71

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