Genetic Variant NM_006228.5:c.184A>G (chr8-28339097-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006228.5(PNOC):c.184A>G(p.Thr62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T62S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PNOC
NM_006228.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1673404).

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.184A>G	p.Thr62Ala	missense	Exon 3 of 4	NP_006219.1	Q13519-1
	PNOC	NM_001284244.2		c.-9A>G		5_prime_UTR	Exon 2 of 3	NP_001271173.1	Q13519-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNOC	ENST00000301908.8	TSL:1 MANE Select	c.184A>G	p.Thr62Ala	missense	Exon 3 of 4	ENSP00000301908.3	Q13519-1
PNOC	ENST00000923262.1		c.184A>G	p.Thr62Ala	missense	Exon 3 of 3	ENSP00000593321.1
PNOC	ENST00000518479.5	TSL:4	c.184A>G	p.Thr62Ala	missense	Exon 3 of 3	ENSP00000428059.1	E7EVP0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33324

American (AMR)

AF:

0.00

AC:

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39412

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105352

Other (OTH)

AF:

0.00

AC:

AN:

59932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.030

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.74

M_CAP

Benign

0.021

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

PhyloP100

1.5

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

REVEL

Benign

0.066

Sift

Benign

0.054

Sift4G

Benign

0.45

Polyphen

0.11

Vest4

0.13

MutPred

0.45

Gain of MoRF binding (P = 0.0994)

MVP

0.63

MPC

0.30

ClinPred

0.25

GERP RS

2.4

PromoterAI

0.021

Neutral

(source)

Varity_R

0.042

gMVP

0.22

Mutation Taster

=80/20

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over