Variant 11-124023323-A-G 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.311A>G(p.His104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,585,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

OR10G9
NM_001001953.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.240

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=0.0462797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10G9	NM_001001953.1 linkuse as main transcript	c.311A>G	p.His104Arg	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.311A>G	p.His104Arg	missense_variant	1/1		NM_001001953.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000221

AC:

AN:

149200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000978

GnomAD3 exomes

AF:

0.0000741

AC:

AN:

229568

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124852

show subpopulations

Gnomad AFR exome

AF:

0.000998

Gnomad AMR exome

AF:

0.0000933

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000251

AC:

AN:

1436224

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

713556

show subpopulations

Gnomad4 AFR exome

AF:

0.000788

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.000221

AC:

AN:

149318

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

72826

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000968

Alfa

AF:

0.000506

Hom.:

ExAC

AF:

0.000100

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

Oct 05, 2023

The c.311A>G (p.H104R) alteration is located in exon 1 (coding exon 1) of the OR10G9 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the histidine (H) at amino acid position 104 to be replaced by an arginine (R). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

0.092

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.78

M_CAP

Benign

0.00082

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.11

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0050

Polyphen

0.93

Vest4

0.38

MVP

0.45

MPC

0.94

ClinPred

0.26

GERP RS

3.3

Varity_R

0.84

gMVP

0.32

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