NM_000912.5:c.948C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000912.5(OPRK1):​c.948C>G​(p.Ile316Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I316I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Publications

0 publications found
Variant links:
Genes affected
OPRK1 (HGNC:8154): (opioid receptor kappa 1) This gene encodes an opioid receptor, which is a member of the 7 transmembrane-spanning G protein-coupled receptor family. It functions as a receptor for endogenous ligands, as well as a receptor for various synthetic opioids. Ligand binding results in inhibition of adenylate cyclase activity and neurotransmitter release. This opioid receptor plays a role in the perception of pain and mediating the hypolocomotor, analgesic and aversive actions of synthetic opioids. Variations in this gene have also been associated with alcohol dependence and opiate addiction. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3911394).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRK1NM_000912.5 linkc.948C>G p.Ile316Met missense_variant Exon 4 of 4 ENST00000265572.8 NP_000903.2 P41145-1
OPRK1NM_001318497.2 linkc.948C>G p.Ile316Met missense_variant Exon 4 of 4 NP_001305426.1 P41145A0A5F9ZI09
OPRK1NM_001282904.2 linkc.681C>G p.Ile227Met missense_variant Exon 5 of 5 NP_001269833.1 P41145-2
LOC105375836NR_188096.1 linkn.2204G>C non_coding_transcript_exon_variant Exon 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPRK1ENST00000265572.8 linkc.948C>G p.Ile316Met missense_variant Exon 4 of 4 1 NM_000912.5 ENSP00000265572.3 P41145-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461868
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727226
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1112002
Other (OTH)
AF:
0.00
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;.;T;.;T
Eigen
Benign
0.16
Eigen_PC
Benign
-0.0037
FATHMM_MKL
Benign
0.40
N
LIST_S2
Uncertain
0.97
D;D;.;.;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.39
T;T;T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.2
.;.;M;.;M
PhyloP100
-0.36
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-2.1
.;.;N;N;N
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
.;.;D;D;D
Sift4G
Benign
0.23
T;T;T;T;T
Polyphen
1.0
.;.;D;.;D
Vest4
0.51
MutPred
0.52
.;.;Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);
MVP
0.85
MPC
0.98
ClinPred
0.98
D
GERP RS
-2.2
Varity_R
0.87
gMVP
0.38
Mutation Taster
=51/49
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

Publications

Other links and lift over

dbSNP: rs78517449; hg19: chr8-54142052; API