dbSNP rs76786693: PNOC:p.Ala118Gly (chr8-28339266-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006228.5(PNOC):c.353C>G(p.Ala118Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0098 in 1,608,402 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0078 ( 62 hom., cov: 32)

Exomes 𝑓: 0.010 ( 966 hom. )

Consequence

PNOC
NM_006228.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

7 publications found

Variant links:

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]

PNOC links:

ENSG00000253690 (HGNC:):

ENSG00000253690 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017537773).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PNOC	NM_006228.5 link	c.353C>G	p.Ala118Gly	missense_variant	Exon 3 of 4	ENST00000301908.8	NP_006219.1
PNOC	NM_001284244.2 link	c.161C>G	p.Ala54Gly	missense_variant	Exon 2 of 3		NP_001271173.1
PNOC	XM_005273532.3 link	c.353C>G	p.Ala118Gly	missense_variant	Exon 3 of 4		XP_005273589.1
PNOC	XM_011544559.3 link	c.353C>G	p.Ala118Gly	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 link	c.353C>G	p.Ala118Gly	missense_variant	Exon 3 of 4	1	NM_006228.5	ENSP00000301908.3

Frequencies

GnomAD3 genomes

AF:

0.00783

AC:

1191

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.0953

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.0214

AC:

5367

AN:

250598

AF XY:

0.0245

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0100

AC:

14576

AN:

1456110

Hom.:

966

Cov.:

AF XY:

0.0122

AC XY:

8814

AN XY:

722988

show subpopulations

African (AFR)

AF:

0.000479

AC:

AN:

33382

American (AMR)

AF:

0.000314

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26096

East Asian (EAS)

AF:

0.152

AC:

6017

AN:

39520

South Asian (SAS)

AF:

0.0884

AC:

7606

AN:

86080

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000153

AC:

169

AN:

1107188

Other (OTH)

AF:

0.0120

AC:

724

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

807

1614

2420

3227

4034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00783

AC:

1193

AN:

152292

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

756

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41564

American (AMR)

AF:

0.000784

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.131

AC:

677

AN:

5178

South Asian (SAS)

AF:

0.0960

AC:

463

AN:

4824

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00759

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00570

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0226

AC:

2738

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.046

T;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.84

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.7

.;M;.

PhyloP100

1.4

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.066

Sift

Benign

0.11

T;T;D

Sift4G

Benign

0.43

T;T;T

Polyphen

0.022

.;B;.

Vest4

0.060, 0.20

MPC

0.28

ClinPred

0.0082

GERP RS

2.9

Varity_R

0.064

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over