NM_001012393.5:c.993A>T

Variant names:

• chr11-132420217-T-A
• NM_001012393.5:c.993A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001012393.5(OPCML):​c.993A>T​(p.Leu331Phe) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OPCML NM_001012393.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.685
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091591746).
• BP6: Variant 11-132420217-T-A is Benign according to our data. Variant chr11-132420217-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3204346.Status of the report is criteria_provided_single_submitter, 1 stars.

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.993A>T	p.Leu331Phe	missense	Exon 8 of 8	NP_001012393.1	Q14982-2
	OPCML	NM_001319103.2		c.1041A>T	p.Leu347Phe	missense	Exon 8 of 8	NP_001306032.1	Q14982-4
	OPCML	NM_002545.5		c.1014A>T	p.Leu338Phe	missense	Exon 7 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.993A>T	p.Leu331Phe	missense	Exon 8 of 8	ENSP00000434750.1	Q14982-2
	OPCML	ENST00000331898.11	TSL:1	c.1014A>T	p.Leu338Phe	missense	Exon 7 of 7	ENSP00000330862.7	Q14982-1
	OPCML	ENST00000374778.4	TSL:1	c.891A>T	p.Leu297Phe	missense	Exon 8 of 8	ENSP00000363910.4	Q14982-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.69
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.050
Sift	Benign	0.48	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.34		Loss of glycosylation at S334 (P = 0.1757)
MVP		0.19
MPC		0.85
ClinPred		0.15	T
GERP RS		3.0
Varity_R		0.048
gMVP		0.53
Mutation Taster		=79/21	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

hg19: chr11-132290111;