Variant 11-124023274-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001953.1(OR10G9):c.262G>A(p.Gly88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,571,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000093 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

OR10G9
NM_001001953.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0260

Variant links:

Genes affected

OR10G9 (HGNC:15129): (olfactory receptor family 10 subfamily G member 9) 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]

OR10G9 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058508784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10G9	NM_001001953.1 linkuse as main transcript	c.262G>A	p.Gly88Ser	missense_variant	1/1	ENST00000375024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10G9	ENST00000375024.1 linkuse as main transcript	c.262G>A	p.Gly88Ser	missense_variant	1/1		NM_001001953.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000931

AC:

AN:

150344

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.000118

AC:

AN:

229650

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

124516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000683

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

153

AN:

1421024

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

705498

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.000206

Gnomad4 ASJ exome

AF:

0.000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000708

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.000238

GnomAD4 genome

AF:

0.0000930

AC:

AN:

150460

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

73414

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.0000666

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.0000868

Hom.:

ExAC

AF:

0.000125

AC:

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

Mar 14, 2023

The c.262G>A (p.G88S) alteration is located in exon 1 (coding exon 1) of the OR10G9 gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glycine (G) at amino acid position 88 to be replaced by a serine (S). 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

-0.40

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.00059

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.14

M_CAP

Benign

0.0012

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.61

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.80

REVEL

Benign

0.20

Sift

Benign

0.84

Sift4G

Benign

0.74

Polyphen

0.48

Vest4

0.097

MVP

0.22

MPC

0.43

ClinPred

0.064

GERP RS

3.3

Varity_R

0.036

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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