Genetic Variant NM_001004747.2:c.196T>G (chr11-56252449-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004747.2(OR5T3):c.196T>G(p.Trp66Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,802 control chromosomes in the GnomAD database, including 1,316 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 108 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1208 hom. )

Consequence

OR5T3
NM_001004747.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

OR5T3 (HGNC:15297): (olfactory receptor family 5 subfamily T 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]

OR5T3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015727878).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5T3	NM_001004747.2 link	c.196T>G	p.Trp66Gly	missense_variant	Exon 1 of 1	ENST00000313033.4	NP_001004747.2	Q8NGG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5T3	ENST00000313033.4 link	c.196T>G	p.Trp66Gly	missense_variant	Exon 1 of 1	6	NM_001004747.2	ENSP00000323612.3		A0A2C9F2M2

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2120

AN:

152066

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0755

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0356

AC:

8920

AN:

250900

Hom.:

730

AF XY:

0.0282

AC XY:

3821

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.00339

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.00846

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.0221

GnomAD4 exome

AF:

0.0106

AC:

15437

AN:

1461618

Hom.:

1208

Cov.:

AF XY:

0.00964

AC XY:

7009

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.00523

Gnomad4 FIN exome

AF:

0.00755

Gnomad4 NFE exome

AF:

0.000587

Gnomad4 OTH exome

AF:

0.00934

GnomAD4 genome

AF:

0.0139

AC:

2121

AN:

152184

Hom.:

108

Cov.:

AF XY:

0.0158

AC XY:

1179

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.00102

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0103

Hom.:

183

Bravo

AF:

0.0216

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0292

AC:

3540

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.2

N;.

PrimateAI

Benign

0.18

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.047

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0070

D;.

Polyphen

0.0070

B;.

Vest4

0.075

MPC

0.0066

ClinPred

0.0038

GERP RS

-0.032

Varity_R

0.12

gMVP

0.098

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over