chr2-37372684-G-A
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
NM_012413.4 missense, splice_region
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 9.86
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
QPCT | NM_012413.4 | 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 | c.943G>A | p.Val315Ile | missense_variant, splice_region_variant | 7/7 | 1 | NM_012413.4 | P1 | |
QPCT | ENST00000404976.5 | c.796G>A | p.Val266Ile | missense_variant, splice_region_variant | 6/6 | 2 | |||
QPCT | ENST00000444022.1 | c.238G>A | p.Val80Ile | missense_variant, splice_region_variant | 4/4 | 5 | |||
QPCT | ENST00000469098.1 | n.506G>A | splice_region_variant, non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249146Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134604
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1459964Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 726186
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;T;D
Sift4G
Uncertain
T;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of catalytic residue at L320 (P = 0.0631);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at