rs2240228

Variant names:

• chr19-15742062-G-A
• rs2240228
• NM_013938.2:c.670G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15742062-G-A
• chr19-15742062-G-T

Variant summary

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

The NM_013938.2(OR10H3):​c.670G>A​(p.Val224Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,890 control chromosomes in the GnomAD database, including 54,789 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V224A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3907 hom., cov: 31)
  • Exomes 𝑓: 0.26 (50882 hom.)
• Consequence: OR10H3 NM_013938.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 30 publications found

Genes affected

OR10H3 (HGNC:8174): (olfactory receptor family 10 subfamily H 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=0.0048362017).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10H3	NM_013938.2	c.670G>A	p.Val224Met	missense_variant	Exon 2 of 2	ENST00000641646.1	NP_039226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10H3	ENST00000641646.1	c.670G>A	p.Val224Met	missense_variant	Exon 2 of 2		NM_013938.2	ENSP00000493287.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32304 AN: 151906 Hom.: 3907 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.232 AC: 58352 AN: 251466 AF XY: 0.240

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.260 AC: 380009 AN: 1461866 Hom.: 50882 Cov.: 83 AF XY: 0.260 AC XY: 189419 AN XY: 727236

African (AFR) AF: 0.0993 AC: 3326 AN: 33480

American (AMR) AF: 0.158 AC: 7068 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5809 AN: 26136

East Asian (EAS) AF: 0.208 AC: 8265 AN: 39700

South Asian (SAS) AF: 0.271 AC: 23408 AN: 86258

European-Finnish (FIN) AF: 0.277 AC: 14787 AN: 53420

Middle Eastern (MID) AF: 0.299 AC: 1723 AN: 5768

European-Non Finnish (NFE) AF: 0.270 AC: 300317 AN: 1111990

Other (OTH) AF: 0.253 AC: 15306 AN: 60390

GnomAD4 genome AF: 0.213 AC: 32311 AN: 152024 Hom.: 3907 Cov.: 31 AF XY: 0.213 AC XY: 15846 AN XY: 74288

African (AFR) AF: 0.105 AC: 4341 AN: 41488

American (AMR) AF: 0.201 AC: 3075 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1048 AN: 5156

South Asian (SAS) AF: 0.285 AC: 1376 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3056 AN: 10558

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17807 AN: 67952

Other (OTH) AF: 0.246 AC: 519 AN: 2106

Alfa AF: 0.235 Hom.: 17009

Bravo AF: 0.201

TwinsUK AF: 0.273 AC: 1014

ALSPAC AF: 0.264 AC: 1016

ESP6500AA AF: 0.104 AC: 458

ESP6500EA AF: 0.259 AC: 2228

ExAC AF: 0.231 AC: 28088

Asia WGS AF: 0.235 AC: 818 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.74	.;T
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PhyloP100		-2.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.056
Sift	Uncertain	0.028	.;D
Sift4G	Uncertain	0.015	.;D
Polyphen		0.58	P;P
Vest4		0.034
MPC		0.079
ClinPred		0.021	T
GERP RS		2.4
Varity_R		0.14
gMVP		0.061
Mutation Taster		=99/1	polymorphism (auto)

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: rs2240228; hg19: chr19-15852872; COSMIC: COSV59943633;