Genetic Variant OR1L6:p.Met223Thr (chr9-122750515-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004453.3(OR1L6):c.668T>C(p.Met223Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 17)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

OR1L6
NM_001004453.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.200

Publications

0 publications found

Variant links:

Genes affected

OR1L6 (HGNC:8218): (olfactory receptor family 1 subfamily L member 6) 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]

OR1L6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05951819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004453.3. 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
	OR1L6	NM_001004453.3	MANE Select	c.668T>C	p.Met223Thr	missense	Exon 2 of 2	NP_001004453.2	A0A0C4DFP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L6	ENST00000304720.3	TSL:6 MANE Select	c.668T>C	p.Met223Thr	missense	Exon 2 of 2	ENSP00000304235.2	A0A0C4DFP2
	OR1L6	ENST00000373684.1	TSL:6	c.776T>C	p.Met259Thr	missense	Exon 1 of 1	ENSP00000362788.1	Q8NGR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

98672

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000804

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000135

AC:

AN:

740790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

385342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24070

American (AMR)

AF:

0.0000356

AC:

AN:

28056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16652

East Asian (EAS)

AF:

0.00

AC:

AN:

35560

South Asian (SAS)

AF:

0.00

AC:

AN:

58724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

487968

Other (OTH)

AF:

0.00

AC:

AN:

36346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

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

Benign

0.077

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.8

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.16

M_CAP

Benign

0.00098

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-0.20

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.95

REVEL

Benign

0.12

Sift

Benign

0.58

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.053

MutPred

0.49

Loss of stability (P = 0.0301)

MVP

0.21

MPC

0.33

ClinPred

0.038

GERP RS

3.5

Varity_R

0.069

gMVP

0.086

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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