rs2240228

chr19-15742062-G-Achr19-15742062-G-T

Variant summary

Our verdict is Benign. Variant got -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. 11/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
OR10H3	NM_013938.2	c.670G>A	p.Val224Met	missense_variant	2/2	ENST00000641646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10H3	ENST00000641646.1	c.670G>A	p.Val224Met	missense_variant	2/2		NM_013938.2	P1

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

GnomAD3 exomes AF: 0.232 AC: 58352 AN: 251466 Hom.: 7282 AF XY: 0.240 AC XY: 32572 AN XY: 135898

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 SAS exome AF: 0.272

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

Gnomad4 AFR exome AF: 0.0993

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.253

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.246

Alfa AF: 0.240 Hom.: 7078

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
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.97	P
PrimateAI	Benign	0.22	T
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

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

Other links and lift over

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