Variant 11-123977124-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004474.2(OR10S1):c.541T>C(p.Tyr181His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,614,226 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 10 hom. )

Consequence

OR10S1
NM_001004474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.985

Variant links:

Genes affected

OR10S1 (HGNC:14807): (olfactory receptor family 10 subfamily S member 1) 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]

OR10S1 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=0.0057314634).

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10S1	NM_001004474.2 linkuse as main transcript	c.541T>C	p.Tyr181His	missense_variant	1/1	ENST00000641123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10S1	ENST00000641123.1 linkuse as main transcript	c.541T>C	p.Tyr181His	missense_variant	1/1		NM_001004474.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

261

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00162

AC:

407

AN:

251462

Hom.:

AF XY:

0.00155

AC XY:

210

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00351

AC:

5125

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2427

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00432

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152350

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

127

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00259

Hom.:

Bravo

AF:

0.00196

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00129

AC:

157

EpiCase

AF:

0.00300

EpiControl

AF:

0.00314

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 01, 2021

The c.568T>C (p.Y190H) alteration is located in exon 1 (coding exon 1) of the OR10S1 gene. This alteration results from a T to C substitution at nucleotide position 568, causing the tyrosine (Y) at amino acid position 190 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

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.00046

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.50

.;N

REVEL

Benign

0.12

Sift

Benign

0.58

.;T

Sift4G

Benign

0.88

.;T

Polyphen

0.065

.;B

Vest4

0.11

MVP

0.13

MPC

0.16

ClinPred

0.0059

GERP RS

3.9

Varity_R

0.060

gMVP

0.23

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