Variant chr19-15794287-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004466.2(OR10H5):c.239G>A(p.Arg80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,612,556 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 4 hom. )

Consequence

OR10H5
NM_001004466.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

Variant links:

Genes affected

OR10H5 (HGNC:15389): (olfactory receptor family 10 subfamily H member 5) 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]

OR10H5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014201254).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10H5	NM_001004466.2 linkuse as main transcript	c.239G>A	p.Arg80His	missense_variant	2/2	ENST00000642092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10H5	ENST00000642092.2 linkuse as main transcript	c.239G>A	p.Arg80His	missense_variant	2/2		NM_001004466.2	P1
OR10H5	ENST00000308940.8 linkuse as main transcript	c.239G>A	p.Arg80His	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

150760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00551

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000279

AC:

AN:

250890

Hom.:

AF XY:

0.000332

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000227

AC:

332

AN:

1461676

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

174

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000194

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000186

AC:

AN:

150880

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

73636

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000212

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.239G>A (p.R80H) alteration is located in exon 1 (coding exon 1) of the OR10H5 gene. This alteration results from a G to A substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.1

.;D

REVEL

Benign

0.056

Sift

Uncertain

0.013

.;D

Sift4G

Uncertain

0.024

.;D

Polyphen

0.062

B;B

Vest4

0.090

MVP

0.42

MPC

0.36

ClinPred

0.042

GERP RS

-0.12

Varity_R

0.17

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over