Variant chr14-21570309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001005465.2(OR10G3):c.436G>A(p.Val146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000308 in 1,614,084 control chromosomes in the GnomAD database, including 3 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 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

OR10G3
NM_001005465.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.386

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016079605).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10G3	NM_001005465.2 linkuse as main transcript	c.436G>A	p.Val146Met	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.436G>A	p.Val146Met	missense_variant	2/2	NM_001005465.2	ENSP00000493245	P1
OR10G3	ENST00000641185.1 linkuse as main transcript	c.436G>A	p.Val146Met	missense_variant	3/3		ENSP00000492973	P1
OR10G3	ENST00000641655.1 linkuse as main transcript	n.292-228G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000374

AC:

AN:

251346

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000312

AC:

456

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

236

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000269

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000518

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

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

Nov 07, 2022

The c.436G>A (p.V146M) alteration is located in exon 1 (coding exon 1) of the OR10G3 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). 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

0.25

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

T;T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.079

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.0036

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.86

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.4

.;.;N

REVEL

Benign

0.14

Sift

Benign

0.095

.;.;T

Sift4G

Benign

0.063

.;.;T

Polyphen

0.76

P;P;P

Vest4

0.13

MVP

0.41

MPC

0.29

ClinPred

0.11

GERP RS

4.6

Varity_R

0.17

gMVP

0.19

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