rs2230299

Positions:

• chr2-37352794-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012413.4(QPCT):​c.126C>T​(p.Tyr42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,298 control chromosomes in the GnomAD database, including 19,126 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.

• Frequency:
  • Genomes: 𝑓 0.21 (6218 hom., cov: 33)
  • Exomes 𝑓: 0.085 (12908 hom.)
• Consequence: QPCT NM_012413.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.143 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QPCT	NM_012413.4	c.126C>T	p.Tyr42=	synonymous_variant	2/7	ENST00000338415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QPCT	ENST00000338415.8	c.126C>T	p.Tyr42=	synonymous_variant	2/7	1	NM_012413.4	P1
QPCT	ENST00000650442.1	c.-67C>T		5_prime_UTR_variant	2/4
QPCT	ENST00000404976.5	c.121-6786C>T		intron_variant		2
QPCT	ENST00000470075.1	n.130C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32042 AN: 152048 Hom.: 6205 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.164 AC: 41164 AN: 251294 Hom.: 6485 AF XY: 0.144 AC XY: 19590 AN XY: 135824

Gnomad AFR exome AF: 0.497

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0492

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.0850 AC: 124148 AN: 1461132 Hom.: 12908 Cov.: 31 AF XY: 0.0831 AC XY: 60409 AN XY: 726770

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0458

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.211 AC: 32110 AN: 152166 Hom.: 6218 Cov.: 33 AF XY: 0.213 AC XY: 15838 AN XY: 74386

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0483

Gnomad4 OTH AF: 0.197

Alfa AF: 0.109 Hom.: 1375

Bravo AF: 0.241

Asia WGS AF: 0.235 AC: 816 AN: 3478

EpiCase AF: 0.0476

EpiControl AF: 0.0462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2230299; hg19: chr2-37579937; COSMIC: COSV58119314;