Genetic Variant LKAAEAR1:p.Gln145Arg (chr20-64083674-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001353425.2(LKAAEAR1):c.434A>G(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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LKAAEAR1
NM_001353425.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.973

Publications

0 publications found

Variant links:

Genes affected

LKAAEAR1 (HGNC:33718): (LKAAEAR motif containing 1)

LKAAEAR1 links:

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]

OPRL1 links:

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ACMG classification

Classification was made for transcript

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=0.30149886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353425.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LKAAEAR1	NM_001353425.2	MANE Select	c.434A>G	p.Gln145Arg	missense	Exon 2 of 3	NP_001340354.1	Q8TD35-1
OPRL1	NM_182647.4	MANE Select	c.-185+3322T>C		intron	N/A	NP_872588.1	P41146-1
LKAAEAR1	NM_001007125.3		c.434A>G	p.Gln145Arg	missense	Exon 2 of 2	NP_001007126.1	Q8TD35-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LKAAEAR1	ENST00000302096.5	TSL:2 MANE Select	c.434A>G	p.Gln145Arg	missense	Exon 2 of 3	ENSP00000302763.4	Q8TD35-1
LKAAEAR1	ENST00000308906.6	TSL:1	c.434A>G	p.Gln145Arg	missense	Exon 2 of 2	ENSP00000310801.2	Q8TD35-2
OPRL1	ENST00000336866.7	TSL:5 MANE Select	c.-185+3322T>C		intron	N/A	ENSP00000336843.2	P41146-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1276442

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

623120

African (AFR)

AF:

0.00

AC:

AN:

24922

American (AMR)

AF:

0.00

AC:

AN:

18364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19696

East Asian (EAS)

AF:

0.00

AC:

AN:

28690

South Asian (SAS)

AF:

0.00

AC:

AN:

64600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4140

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1030498

Other (OTH)

AF:

0.00

AC:

AN:

52784

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

0.048

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

PhyloP100

0.97

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.43

MutPred

0.17

Loss of ubiquitination at K146 (P = 0.0481)

MVP

0.28

MPC

0.82

ClinPred

0.98

GERP RS

4.1

Varity_R

0.74

gMVP

0.060

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over