rs857703

Variant names:

• chr1-158717434-G-A
• rs857703
• NM_001005327.3:c.682C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005327.3(OR6K3):​c.682C>T​(p.Pro228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,613,112 control chromosomes in the GnomAD database, including 112,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.32 (8911 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103251 hom.)
• Consequence: OR6K3 NM_001005327.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796
• Publications: 26 publications found

Genes affected

OR6K3 (HGNC:15030): (olfactory receptor family 6 subfamily K member 3) 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8157234E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6K3	NM_001005327.3	c.682C>T	p.Pro228Ser	missense_variant	Exon 2 of 2	ENST00000368145.2	NP_001005327.2
OR6K3	XM_047420296.1	c.682C>T	p.Pro228Ser	missense_variant	Exon 3 of 3		XP_047276252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6K3	ENST00000368145.2	c.682C>T	p.Pro228Ser	missense_variant	Exon 2 of 2	6	NM_001005327.3	ENSP00000357127.1
OR6K3	ENST00000368146.1	c.730C>T	p.Pro244Ser	missense_variant	Exon 1 of 1	6		ENSP00000357128.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47974 AN: 151822 Hom.: 8912 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.336

GnomAD2 exomes AF: 0.362 AC: 90603 AN: 250278 AF XY: 0.359

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.436

Gnomad FIN exome AF: 0.474

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.370 AC: 541214 AN: 1461172 Hom.: 103251 Cov.: 37 AF XY: 0.366 AC XY: 266281 AN XY: 726896

African (AFR) AF: 0.115 AC: 3837 AN: 33440

American (AMR) AF: 0.399 AC: 17810 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9015 AN: 26120

East Asian (EAS) AF: 0.402 AC: 15943 AN: 39686

South Asian (SAS) AF: 0.220 AC: 18998 AN: 86254

European-Finnish (FIN) AF: 0.476 AC: 25437 AN: 53402

Middle Eastern (MID) AF: 0.342 AC: 1970 AN: 5760

European-Non Finnish (NFE) AF: 0.384 AC: 426325 AN: 1111472

Other (OTH) AF: 0.362 AC: 21879 AN: 60368

GnomAD4 genome AF: 0.316 AC: 47978 AN: 151940 Hom.: 8911 Cov.: 31 AF XY: 0.321 AC XY: 23825 AN XY: 74256

African (AFR) AF: 0.128 AC: 5323 AN: 41494

American (AMR) AF: 0.374 AC: 5696 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2257 AN: 5124

South Asian (SAS) AF: 0.204 AC: 982 AN: 4818

European-Finnish (FIN) AF: 0.482 AC: 5093 AN: 10568

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26297 AN: 67938

Other (OTH) AF: 0.339 AC: 715 AN: 2112

Alfa AF: 0.361 Hom.: 40594

Bravo AF: 0.307

TwinsUK AF: 0.371 AC: 1374

ALSPAC AF: 0.382 AC: 1472

ESP6500AA AF: 0.134 AC: 589

ESP6500EA AF: 0.378 AC: 3247

ExAC AF: 0.356 AC: 43215

Asia WGS AF: 0.317 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.0099	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.098	T;T
MetaRNN	Benign	0.00028	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L
PhyloP100		0.80
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.028
Sift	Benign	0.10	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.080	.;B
Vest4		0.078
MPC		0.055
ClinPred		0.0052	T
GERP RS		0.81
Varity_R		0.082
gMVP		0.075
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs857703; hg19: chr1-158687224; COSMIC: COSV63745437;