11-132420213-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001012393.5(OPCML):c.997C>T(p.His333Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
OPCML
NM_001012393.5 missense
NM_001012393.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.76
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04417464).
BS2
?
High AC in GnomAdExome at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPCML | NM_001012393.5 | c.997C>T | p.His333Tyr | missense_variant | 8/8 | ENST00000524381.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPCML | ENST00000524381.6 | c.997C>T | p.His333Tyr | missense_variant | 8/8 | 1 | NM_001012393.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000685 AC: 17AN: 248352Hom.: 0 AF XY: 0.0000967 AC XY: 13AN XY: 134402
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461612Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727118
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2023 | The c.1018C>T (p.H340Y) alteration is located in exon 7 (coding exon 7) of the OPCML gene. This alteration results from a C to T substitution at nucleotide position 1018, causing the histidine (H) at amino acid position 340 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N
REVEL
Benign
Sift
Benign
T;.;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0072);Loss of disorder (P = 0.0072);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at