Variant chr19-9126023-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_001001958.1(OR7G3):c.928T>C(p.Ser310Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000792 in 1,502,796 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 0.00022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

OR7G3
NM_001001958.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

Variant links:

Genes affected

OR7G3 (HGNC:8467): (olfactory receptor family 7 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]

OR7G3 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=0.007301897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7G3	NM_001001958.1 linkuse as main transcript	c.928T>C	p.Ser310Pro	missense_variant	1/1	ENST00000305444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7G3	ENST00000305444.2 linkuse as main transcript	c.928T>C	p.Ser310Pro	missense_variant	1/1		NM_001001958.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

58132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000125

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000261

AC:

AN:

114856

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

62404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00588

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000559

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000734

AC:

106

AN:

1444664

Hom.:

Cov.:

AF XY:

0.0000824

AC XY:

AN XY:

716362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00308

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000727

Gnomad4 OTH exome

AF:

0.000285

GnomAD4 genome

AF:

0.000224

AC:

AN:

58132

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

28774

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000125

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000307

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000942

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

Dec 12, 2023

The c.928T>C (p.S310P) alteration is located in exon 1 (coding exon 1) of the OR7G3 gene. This alteration results from a T to C substitution at nucleotide position 928, causing the serine (S) at amino acid position 310 to be replaced by a proline (P). 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

0.073

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.7

DANN

Benign

0.89

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.26

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

REVEL

Benign

0.014

Sift

Benign

0.051

Sift4G

Uncertain

0.047

Polyphen

0.011

Vest4

0.086

MutPred

0.34

Loss of MoRF binding (P = 0.0224);

MVP

0.15

MPC

0.11

ClinPred

0.016

GERP RS

-0.63

Varity_R

0.21

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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