chr11-132436204-T-G

Variant names:

• chr11-132436204-T-G
• rs2096012407
• NM_001012393.5:c.798A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012393.5(OPCML):​c.798A>C​(p.Glu266Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OPCML NM_001012393.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

OPCML (HGNC:8143): (opioid binding protein/cell adhesion molecule like) This gene encodes a member of the IgLON subfamily in the immunoglobulin protein superfamily of proteins. The encoded preprotein is proteolytically processed to generate the mature protein. This protein is localized in the plasma membrane and may have an accessory role in opioid receptor function. This gene has an ortholog in rat and bovine. The opioid binding-cell adhesion molecule encoded by the rat gene binds opioid alkaloids in the presence of acidic lipids, exhibits selectivity for mu ligands and acts as a GPI-anchored protein. Since the encoded protein is highly conserved in species during evolution, it may have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

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=0.2669312).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	NM_001012393.5	MANE Select	c.798A>C	p.Glu266Asp	missense	Exon 7 of 8	NP_001012393.1	Q14982-2
	OPCML	NM_001319103.2		c.819A>C	p.Glu273Asp	missense	Exon 6 of 8	NP_001306032.1	Q14982-4
	OPCML	NM_002545.5		c.819A>C	p.Glu273Asp	missense	Exon 6 of 7	NP_002536.1	A8K0Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPCML	ENST00000524381.6	TSL:1 MANE Select	c.798A>C	p.Glu266Asp	missense	Exon 7 of 8	ENSP00000434750.1	Q14982-2
	OPCML	ENST00000331898.11	TSL:1	c.819A>C	p.Glu273Asp	missense	Exon 6 of 7	ENSP00000330862.7	Q14982-1
	OPCML	ENST00000374778.4	TSL:1	c.696A>C	p.Glu232Asp	missense	Exon 7 of 8	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	-0.085	N
PhyloP100		1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.057	T
Polyphen		0.94	P
Vest4		0.35
MutPred		0.41		Gain of ubiquitination at K275 (P = 0.0975)
MVP		0.69
MPC		1.8
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.53
gMVP		0.46
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs2096012407; hg19: chr11-132306098;