Variant 8-53250943-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000912.5(OPRK1):c.95G>T(p.Gly32Val) 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 1,458,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.869

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]

OPRK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14658764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OPRK1	NM_000912.5 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant	2/4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant	2/4		NP_001305426.1
OPRK1	NM_001282904.2 linkuse as main transcript	c.-347G>T		5_prime_UTR_variant	2/5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant	2/4	1	NM_000912.5	ENSP00000265572	P1	P41145-1
OPRK1	ENST00000520287.5 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant	1/3	1		ENSP00000429706	P1	P41145-1
OPRK1	ENST00000522508.1 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000428231
OPRK1	ENST00000673285.2 linkuse as main transcript	c.95G>T	p.Gly32Val	missense_variant	2/4			ENSP00000500765

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.95G>T (p.G32V) alteration is located in exon 2 (coding exon 1) of the OPRK1 gene. This alteration results from a G to T substitution at nucleotide position 95, causing the glycine (G) at amino acid position 32 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.56

.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.69

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.047

Sift

Benign

0.035

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.0

B;B

Vest4

0.24

MutPred

0.39

Loss of disorder (P = 0.0972);Loss of disorder (P = 0.0972);

MVP

0.81

MPC

0.47

ClinPred

0.066

GERP RS

1.6

Varity_R

0.058

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over