Genetic Variant OR1K1:p.Val110Ile (chr9-122800450-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080859.1(OR1K1):c.328G>A(p.Val110Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OR1K1
NM_080859.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.514

Variant links:

Genes affected

OR1K1 (HGNC:8212): (olfactory receptor family 1 subfamily K member 1) 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]

OR1K1 links:

PDCL (HGNC:8770): (phosducin like) Phosducin-like protein is a putative modulator of heterotrimeric G proteins. The protein shares extensive amino acid sequence homology with phosducin, a phosphoprotein expressed in retina and pineal gland. Both phosducin-like protein and phosphoducin have been shown to regulate G-protein signaling by binding to the beta-gamma subunits of G proteins. [provided by RefSeq, Jul 2008]

PDCL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025466233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1K1	NM_080859.1 link	c.328G>A	p.Val110Ile	missense_variant	Exon 1 of 1	ENST00000277309.3	NP_543135.1	Q8NGR3A0A126GVB9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1K1	ENST00000277309.3 link	c.328G>A	p.Val110Ile	missense_variant	Exon 1 of 1	6	NM_080859.1	ENSP00000277309.2		Q8NGR3
PDCL	ENST00000436632.5 link	c.253-1911C>T		intron_variant	Intron 2 of 2	3		ENSP00000397984.1		H0Y5D3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250258

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459876

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328G>A (p.V110I) alteration is located in exon 1 (coding exon 1) of the OR1K1 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the valine (V) at amino acid position 110 to be replaced by an isoleucine (I). 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

0.082

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.36

DANN

Benign

0.54

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.10

M_CAP

Benign

0.0081

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.35

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.050

REVEL

Benign

0.034

Sift

Benign

0.63

Sift4G

Benign

0.44

Polyphen

0.0060

Vest4

0.027

MutPred

0.32

Loss of catalytic residue at V110 (P = 0.0121);

MVP

0.11

MPC

0.066

ClinPred

0.13

GERP RS

0.70

Varity_R

0.036

gMVP

0.048

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

Other links and lift over