NM_012413.4:c.723+974A>C

Variant names:

• chr2-37368382-A-C
• rs3770748
• NM_012413.4:c.723+974A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012413.4(QPCT):​c.723+974A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: QPCT NM_012413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QPCT	NM_012413.4	c.723+974A>C		intron_variant	Intron 4 of 6	ENST00000338415.8	NP_036545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QPCT	ENST00000338415.8	c.723+974A>C		intron_variant	Intron 4 of 6	1	NM_012413.4	ENSP00000344829.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 44248 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 25074

African (AFR) AF: 0.00 AC: 0 AN: 546

American (AMR) AF: 0.00 AC: 0 AN: 1206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 898

East Asian (EAS) AF: 0.00 AC: 0 AN: 776

South Asian (SAS) AF: 0.00 AC: 0 AN: 10180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 25002

Other (OTH) AF: 0.00 AC: 0 AN: 2234

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 2735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-0.052
PromoterAI		-0.014	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3770748; hg19: chr2-37595525;