20-64083674-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001353425.2(LKAAEAR1):āc.434A>Gā(p.Gln145Arg) 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LKAAEAR1
NM_001353425.2 missense
NM_001353425.2 missense
Scores
4
6
8
Clinical Significance
Conservation
PhyloP100: 0.973
Genes affected
LKAAEAR1 (HGNC:33718): (LKAAEAR motif containing 1)
OPRL1 (HGNC:8155): (opioid related nociceptin receptor 1) The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5'-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described 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]
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ACMG classification
Classification made for transcript
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=0.30149886).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LKAAEAR1 | NM_001353425.2 | c.434A>G | p.Gln145Arg | missense_variant | 2/3 | ENST00000302096.5 | NP_001340354.1 | |
OPRL1 | NM_182647.4 | c.-185+3322T>C | intron_variant | ENST00000336866.7 | NP_872588.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LKAAEAR1 | ENST00000302096.5 | c.434A>G | p.Gln145Arg | missense_variant | 2/3 | 2 | NM_001353425.2 | ENSP00000302763 | P1 | |
OPRL1 | ENST00000336866.7 | c.-185+3322T>C | intron_variant | 5 | NM_182647.4 | ENSP00000336843 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1276442Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0AN XY: 623120
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1276442
Hom.:
Cov.:
38
AF XY:
AC XY:
0
AN XY:
623120
Gnomad4 AFR exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 | Nov 13, 2023 | The c.434A>G (p.Q145R) alteration is located in exon 2 (coding exon 2) of the LKAAEAR1 gene. This alteration results from a A to G substitution at nucleotide position 434, causing the glutamine (Q) at amino acid position 145 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;D;D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of ubiquitination at K146 (P = 0.0481);Loss of ubiquitination at K146 (P = 0.0481);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.