NM_006228.5:c.500G>C

Variant names:

• chr8-28339413-G-C
• rs1411574692
• NM_006228.5:c.500G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006228.5(PNOC):​c.500G>C​(p.Arg167Pro) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNOC NM_006228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

Genes affected

PNOC (HGNC:9163): (prepronociceptin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include nociceptin, nocistatin, and orphanin FQ2 (OFQ2). Nociceptin, also known as orphanin FQ, is a 17-amino acid neuropeptide that binds to the nociceptin receptor to induce increased pain sensitivity, and may additionally regulate body temperature, learning and memory, and hunger. Another product of the encoded preproprotein, nocistatin, may inhibit the effects of nociceptin. [provided by RefSeq, Jul 2015]

ENSG00000253690 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNOC	NM_006228.5	c.500G>C	p.Arg167Pro	missense_variant	Exon 3 of 4	ENST00000301908.8	NP_006219.1
PNOC	NM_001284244.2	c.308G>C	p.Arg103Pro	missense_variant	Exon 2 of 3		NP_001271173.1
PNOC	XM_005273532.3	c.500G>C	p.Arg167Pro	missense_variant	Exon 3 of 4		XP_005273589.1
PNOC	XM_011544559.3	c.500G>C	p.Arg167Pro	missense_variant	Exon 3 of 4		XP_011542861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNOC	ENST00000301908.8	c.500G>C	p.Arg167Pro	missense_variant	Exon 3 of 4	1	NM_006228.5	ENSP00000301908.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.56	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.30		Gain of glycosylation at R167 (P = 0.0242);.;
MVP		0.80
MPC		0.99
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs1411574692; hg19: chr8-28196930;