chr8-53229492-G-C

Variant names:

• chr8-53229492-G-C
• NM_000912.5:c.948C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OPRK1 NM_000912.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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 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
OPRK1	NM_000912.5	c.948C>G	p.Ile316Met	missense_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.948C>G	p.Ile316Met	missense_variant	Exon 4 of 4		NP_001305426.1
OPRK1	NM_001282904.2	c.681C>G	p.Ile227Met	missense_variant	Exon 5 of 5		NP_001269833.1
LOC105375836	NR_188096.1	n.2204G>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.948C>G	p.Ile316Met	missense_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3

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

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.: 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
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

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.

Other links and lift over

hg19: chr8-54142052;