chr8-28339218-G-A

Variant names:

• chr8-28339218-G-A
• rs151278852
• NM_006228.5:c.305G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006228.5(PNOC):​c.305G>A​(p.Arg102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PNOC NM_006228.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10332459).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006228.5. 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
	PNOC	NM_006228.5	MANE Select	c.305G>A	p.Arg102Gln	missense	Exon 3 of 4	NP_006219.1	Q13519-1
	PNOC	NM_001284244.2		c.113G>A	p.Arg38Gln	missense	Exon 2 of 3	NP_001271173.1	Q13519-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNOC	ENST00000301908.8	TSL:1 MANE Select	c.305G>A	p.Arg102Gln	missense	Exon 3 of 4	ENSP00000301908.3	Q13519-1
	PNOC	ENST00000923262.1		c.305G>A	p.Arg102Gln	missense	Exon 3 of 3	ENSP00000593321.1
	PNOC	ENST00000518479.5	TSL:4	c.305G>A	p.Arg102Gln	missense	Exon 3 of 3	ENSP00000428059.1	E7EVP0

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250852 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460178 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726012

African (AFR) AF: 0.000239 AC: 8 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110560

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74356

African (AFR) AF: 0.000290 AC: 12 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.7
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.079
Sift	Benign	0.17	T
Sift4G	Benign	0.17	T
Polyphen		0.49	P
Vest4		0.17
MVP		0.58
MPC		0.31
ClinPred		0.042	T
GERP RS		1.0
Varity_R		0.034
gMVP		0.28
Mutation Taster		=88/12	polymorphism

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: rs151278852; hg19: chr8-28196735;