2-37352828-C-T

Variant names:

• chr2-37352828-C-T
• rs2255991
• NM_012413.4:c.160C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012413.4(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. Synonymous variant affecting the same amino acid position (i.e. R54R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.061 (839 hom., cov: 32)
  • Exomes 𝑓: 0.034 (5718 hom.)
• Consequence: QPCT NM_012413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 24 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCT	NM_012413.4	MANE Select	c.160C>T	p.Arg54Trp	missense	Exon 2 of 7	NP_036545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPCT	ENST00000338415.8	TSL:1 MANE Select	c.160C>T	p.Arg54Trp	missense	Exon 2 of 7	ENSP00000344829.3
	QPCT	ENST00000650442.1		c.-33C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000498156.1
	QPCT	ENST00000952068.1		c.160C>T	p.Arg54Trp	missense	Exon 2 of 7	ENSP00000622127.1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9215 AN: 152108 Hom.: 844 Cov.: 32

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

GnomAD2 exomes AF: 0.0970 AC: 24392 AN: 251434 AF XY: 0.0841

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 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.: 31 AF XY: 0.0329 AC XY: 23944 AN XY: 727178

African (AFR) AF: 0.0594 AC: 1988 AN: 33476

American (AMR) AF: 0.325 AC: 14551 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00738 AC: 193 AN: 26136

East Asian (EAS) AF: 0.341 AC: 13529 AN: 39696

South Asian (SAS) AF: 0.0619 AC: 5340 AN: 86238

European-Finnish (FIN) AF: 0.0774 AC: 4132 AN: 53412

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.00591 AC: 6573 AN: 1111946

Other (OTH) AF: 0.0443 AC: 2673 AN: 60388

GnomAD4 genome AF: 0.0607 AC: 9237 AN: 152226 Hom.: 839 Cov.: 32 AF XY: 0.0685 AC XY: 5097 AN XY: 74416

African (AFR) AF: 0.0601 AC: 2496 AN: 41542

American (AMR) AF: 0.194 AC: 2972 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1791 AN: 5168

South Asian (SAS) AF: 0.0732 AC: 353 AN: 4822

European-Finnish (FIN) AF: 0.0804 AC: 851 AN: 10586

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00888 AC: 604 AN: 68032

Other (OTH) AF: 0.0668 AC: 141 AN: 2110

Alfa AF: 0.0342 Hom.: 2420

Bravo AF: 0.0747

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.0552 AC: 243

ESP6500EA AF: 0.00791 AC: 68

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.063
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.8
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.086
MPC		0.018
ClinPred		0.032	T
GERP RS		4.8
Varity_R		0.29
gMVP		0.68
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2255991; hg19: chr2-37579971; COSMIC: COSV58119325;