Variant rs76786693 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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:

PNOC (HGNC:):

PNOC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PNOC	NM_006228.5 linkuse as main transcript	c.353C>G	p.Ala118Gly	missense_variant	3/4	ENST00000301908.8	NP_006219.1	Q13519-1
PNOC	NM_001284244.2 linkuse as main transcript	c.161C>G	p.Ala54Gly	missense_variant	2/3		NP_001271173.1	Q13519-2
PNOC	XM_005273532.3 linkuse as main transcript	c.353C>G	p.Ala118Gly	missense_variant	3/4		XP_005273589.1
PNOC	XM_011544559.3 linkuse as main transcript	c.353C>G	p.Ala118Gly	missense_variant	3/4		XP_011542861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNOC	ENST00000301908.8 linkuse as main transcript	c.353C>G	p.Ala118Gly	missense_variant	3/4	1	NM_006228.5	ENSP00000301908.3		Q13519-1

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

GnomAD3 exomes

AF:

0.0214

AC:

5367

AN:

250598

Hom.:

312

AF XY:

0.0245

AC XY:

3325

AN XY:

135462

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 SAS exome

AF:

0.0993

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

Gnomad4 AFR exome

AF:

0.000479

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.0884

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00783

AC:

1193

AN:

152292

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

756

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.0960

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00759

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

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;.

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over