Variant 14-21569906-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005465.2(OR10G3):c.839T>C(p.Ile280Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000049 in 1,613,016 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

OR10G3
NM_001005465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

OR10G3 (HGNC:8171): (olfactory receptor family 10 subfamily G member 3) 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]

OR10G3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086844414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10G3	NM_001005465.2 linkuse as main transcript	c.839T>C	p.Ile280Thr	missense_variant	2/2	ENST00000641040.1	NP_001005465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
OR10G3	ENST00000641040.1 linkuse as main transcript	c.839T>C	p.Ile280Thr	missense_variant	2/2	NM_001005465.2	ENSP00000493245	P1
OR10G3	ENST00000641185.1 linkuse as main transcript	c.839T>C	p.Ile280Thr	missense_variant	3/3		ENSP00000492973	P1
OR10G3	ENST00000641655.1 linkuse as main transcript	n.467T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000943

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250324

Hom.:

AF XY:

0.0000813

AC XY:

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00

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:

0.0000267

AC:

AN:

1460888

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000166

GnomAD4 genome

AF:

0.000263

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000940

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000437

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

Aug 09, 2021

The c.839T>C (p.I280T) alteration is located in exon 1 (coding exon 1) of the OR10G3 gene. This alteration results from a T to C substitution at nucleotide position 839, causing the isoleucine (I) at amino acid position 280 to be replaced by a threonine (T). 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

0.58

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.45

.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

0.97

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.3

.;.;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

.;.;D

Sift4G

Uncertain

0.0020

.;.;D

Polyphen

0.93

P;P;P

Vest4

0.42

MVP

0.64

MPC

0.11

ClinPred

0.27

GERP RS

4.8

Varity_R

0.65

gMVP

0.18

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