Variant 9-122568054-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004454.2(OR1L8):c.424T>C(p.Cys142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR1L8
NM_001004454.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

OR1L8 (HGNC:15110): (olfactory receptor family 1 subfamily L member 8) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR1L8 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR1L8	NM_001004454.2 linkuse as main transcript	c.424T>C	p.Cys142Arg	missense_variant	5/5	ENST00000641027.1
OR1L8	XM_017014285.2 linkuse as main transcript	c.424T>C	p.Cys142Arg	missense_variant	3/4
OR1L8	XM_017014286.2 linkuse as main transcript	c.424T>C	p.Cys142Arg	missense_variant	2/2
OR1J2	XR_007061271.1 linkuse as main transcript	n.1541-11899A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1L8	ENST00000641027.1 linkuse as main transcript	c.424T>C	p.Cys142Arg	missense_variant	5/5		NM_001004454.2	P1
	ENST00000431442.2 linkuse as main transcript	n.1363-38592A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251170

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jan 16, 2024

The c.424T>C (p.C142R) alteration is located in exon 1 (coding exon 1) of the OR1L8 gene. This alteration results from a T to C substitution at nucleotide position 424, causing the cysteine (C) at amino acid position 142 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.0016

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-12

.;D

REVEL

Benign

0.10

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.0020

.;D

Polyphen

0.41

B;B

Vest4

0.61

MutPred

0.63

Gain of methylation at C142 (P = 0.0279);Gain of methylation at C142 (P = 0.0279);

MVP

0.69

MPC

0.55

ClinPred

0.99

GERP RS

3.3

Varity_R

0.69

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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