rs34369022

Positions:

• chr8-53229367-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000912.5(OPRK1):​c.1073G>T​(p.Ser358Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: not found (cov: 32)
• Consequence: OPRK1 NM_000912.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

LOC105375836 (HGNC:):

ACMG classification

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=0.21551576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.1073G>T	p.Ser358Ile	missense_variant	4/4	ENST00000265572.8	NP_000903.2
LOC105375836	XR_928877.2	n.2079C>A		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001318497.2	c.1073G>T	p.Ser358Ile	missense_variant	4/4		NP_001305426.1
OPRK1	NM_001282904.2	c.806G>T	p.Ser269Ile	missense_variant	5/5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.1073G>T	p.Ser358Ile	missense_variant	4/4	1	NM_000912.5	ENSP00000265572	P1
	ENST00000524425.1	n.670+12863C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;.;T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.77	T;T;.;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	.;.;M;.;M
MutationTaster	Benign	0.72	D;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	.;.;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.020	.;.;D;D;D
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.0	.;.;B;.;B
Vest4		0.33
MutPred		0.37		.;.;Loss of disorder (P = 0.004);.;Loss of disorder (P = 0.004);
MVP		0.76
MPC		0.39
ClinPred		0.77	D
GERP RS		1.7
Varity_R		0.18
gMVP		0.44

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

Other links and lift over

dbSNP: rs34369022; hg19: chr8-54141927;