rs79344086

Variant names:

• chr1-28859139-C-G
• rs79344086
• NM_000911.4:c.413C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-28859139-C-G
• chr1-28859139-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000911.4(OPRD1):​c.413C>G​(p.Thr138Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T138M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OPRD1 NM_000911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

Genes affected

OPRD1 (HGNC:8153): (opioid receptor delta 1) Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRD1	NM_000911.4	c.413C>G	p.Thr138Arg	missense_variant	Exon 2 of 3	ENST00000234961.7	NP_000902.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRD1	ENST00000234961.7	c.413C>G	p.Thr138Arg	missense_variant	Exon 2 of 3	1	NM_000911.4	ENSP00000234961.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	.;D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	3.7	.;H
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.011	.;D
Sift4G	Uncertain	0.039	D;D
Polyphen		1.0	.;D
Vest4		0.93
MutPred		0.80		Gain of catalytic residue at T138 (P = 0.0058);Gain of catalytic residue at T138 (P = 0.0058);
MVP		0.91
MPC		1.9
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.89
gMVP		0.98

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: rs79344086; hg19: chr1-29185651;