2-37352828-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012413.4(QPCT):​c.160C>G​(p.Arg54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: QPCT NM_012413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Arg54Gly	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>G	p.Arg54Gly	missense	Exon 2 of 7	ENSP00000344829.3
	QPCT	ENST00000650442.1		c.-33C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000498156.1
	QPCT	ENST00000952068.1		c.160C>G	p.Arg54Gly	missense	Exon 2 of 7	ENSP00000622127.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.093
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.8
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.12
Sift	Benign	0.095	T
Sift4G	Benign	0.12	T
Polyphen		0.70	P
Vest4		0.36
MutPred		0.50		Gain of glycosylation at S51 (P = 0.0696)
MVP		0.39
MPC		0.024
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.48
gMVP		0.59
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2255991; hg19: chr2-37579971;