rs2230299

Variant names:

• chr2-37352794-C-T
• rs2230299
• NM_012413.4:c.126C>T
• QPCT p.Tyr42Tyr

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012413.4(QPCT):​c.126C>T​(p.Tyr42Tyr) 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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCT	NM_012413.4	MANE Select	c.126C>T	p.Tyr42Tyr	synonymous	Exon 2 of 7	NP_036545.1	Q16769-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCT	ENST00000338415.8	TSL:1 MANE Select	c.126C>T	p.Tyr42Tyr	synonymous	Exon 2 of 7	ENSP00000344829.3	Q16769-1
	QPCT	ENST00000952068.1		c.126C>T	p.Tyr42Tyr	synonymous	Exon 2 of 7	ENSP00000622127.1
	QPCT	ENST00000952066.1		c.126C>T	p.Tyr42Tyr	synonymous	Exon 2 of 6	ENSP00000622125.1

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

GnomAD2 exomes AF: 0.164 AC: 41164 AN: 251294 AF XY: 0.144

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 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

African (AFR) AF: 0.500 AC: 16732 AN: 33434

American (AMR) AF: 0.371 AC: 16562 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2678 AN: 26124

East Asian (EAS) AF: 0.341 AC: 13502 AN: 39634

South Asian (SAS) AF: 0.119 AC: 10249 AN: 86204

European-Finnish (FIN) AF: 0.111 AC: 5951 AN: 53412

Middle Eastern (MID) AF: 0.0846 AC: 488 AN: 5766

European-Non Finnish (NFE) AF: 0.0458 AC: 50920 AN: 1111510

Other (OTH) AF: 0.117 AC: 7066 AN: 60362

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

African (AFR) AF: 0.488 AC: 20240 AN: 41472

American (AMR) AF: 0.271 AC: 4143 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1797 AN: 5182

South Asian (SAS) AF: 0.131 AC: 634 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1193 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3282 AN: 68004

Other (OTH) AF: 0.197 AC: 417 AN: 2114

Alfa AF: 0.108 Hom.: 1802

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.31
PhyloP100		0.14
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230299;

hg19: chr2-37579937;

COSMIC: COSV58119314;