NM_080859.1:c.328G>A

Variant names:

• chr9-122800450-G-A
• rs750286309
• NM_080859.1:c.328G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 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: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OR1K1 NM_080859.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.514
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025466233).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080859.1. 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
	OR1K1	NM_080859.1	MANE Select	c.328G>A	p.Val110Ile	missense	Exon 1 of 1	NP_543135.1	Q8NGR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1K1	ENST00000277309.3	TSL:6 MANE Select	c.328G>A	p.Val110Ile	missense	Exon 1 of 1	ENSP00000277309.2	Q8NGR3
	PDCL	ENST00000436632.5	TSL:3	c.253-1911C>T		intron	N/A	ENSP00000397984.1	H0Y5D3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250258 AF XY: 0.00000739

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459876 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726344

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.54
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.35	N
PhyloP100		-0.51
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.034
Sift	Benign	0.63	T
Sift4G	Benign	0.44	T
Polyphen		0.0060	B
Vest4		0.027
MutPred		0.32		Loss of catalytic residue at V110 (P = 0.0121)
MVP		0.11
MPC		0.066
ClinPred		0.13	T
GERP RS		0.70
PromoterAI		0.016	Neutral
Varity_R		0.036
gMVP		0.048
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs750286309; hg19: chr9-125562729;