19-15728555-C-T

Variant names:

• chr19-15728555-C-T
• rs1806931
• NM_013939.2:c.512C>T

Variant summary

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

The NM_013939.2(OR10H2):​c.512C>T​(p.Ser171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,613,778 control chromosomes in the GnomAD database, including 14,021 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.086 (1568 hom., cov: 32)
  • Exomes 𝑓: 0.081 (12453 hom.)
• Consequence: OR10H2 NM_013939.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 15 publications found

Genes affected

OR10H2 (HGNC:8173): (olfactory receptor family 10 subfamily H member 2) 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=2.8928684E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013939.2. 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
	OR10H2	NM_013939.2	MANE Select	c.512C>T	p.Ser171Phe	missense	Exon 1 of 1	NP_039227.1	O60403

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10H2	ENST00000305899.5	TSL:6 MANE Select	c.512C>T	p.Ser171Phe	missense	Exon 1 of 1	ENSP00000306095.3	O60403

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13078 AN: 152114 Hom.: 1565 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0833

GnomAD2 exomes AF: 0.139 AC: 34811 AN: 251326 AF XY: 0.126

Gnomad AFR exome AF: 0.0303

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.0520

Gnomad EAS exome AF: 0.562

Gnomad FIN exome AF: 0.0835

Gnomad NFE exome AF: 0.0506

Gnomad OTH exome AF: 0.0967

GnomAD4 exome AF: 0.0809 AC: 118246 AN: 1461546 Hom.: 12453 Cov.: 41 AF XY: 0.0800 AC XY: 58176 AN XY: 726978

African (AFR) AF: 0.0264 AC: 885 AN: 33474

American (AMR) AF: 0.329 AC: 14715 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 1382 AN: 26122

East Asian (EAS) AF: 0.583 AC: 23163 AN: 39698

South Asian (SAS) AF: 0.114 AC: 9833 AN: 86250

European-Finnish (FIN) AF: 0.0822 AC: 4388 AN: 53414

Middle Eastern (MID) AF: 0.0305 AC: 176 AN: 5768

European-Non Finnish (NFE) AF: 0.0523 AC: 58191 AN: 1111722

Other (OTH) AF: 0.0913 AC: 5513 AN: 60386

GnomAD4 genome AF: 0.0860 AC: 13097 AN: 152232 Hom.: 1568 Cov.: 32 AF XY: 0.0932 AC XY: 6936 AN XY: 74420

African (AFR) AF: 0.0314 AC: 1303 AN: 41552

American (AMR) AF: 0.229 AC: 3506 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.571 AC: 2943 AN: 5156

South Asian (SAS) AF: 0.124 AC: 595 AN: 4814

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3515 AN: 68014

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0698 Hom.: 3688

Bravo AF: 0.0965

TwinsUK AF: 0.0477 AC: 177

ALSPAC AF: 0.0610 AC: 235

ESP6500AA AF: 0.0329 AC: 145

ESP6500EA AF: 0.0549 AC: 472

ExAC AF: 0.127 AC: 15356

Asia WGS AF: 0.316 AC: 1096 AN: 3478

EpiCase AF: 0.0464

EpiControl AF: 0.0456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.000029	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.86
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.019
Sift	Benign	0.034	D
Sift4G	Uncertain	0.031	D
Polyphen		0.73	P
Vest4		0.076
MPC		0.60
ClinPred		0.067	T
GERP RS		0.98
Varity_R		0.16
gMVP		0.061
Mutation Taster		=100/0	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: rs1806931; hg19: chr19-15839365; COSMIC: COSV104621654;