Variant rs3749971 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030959.3(OR12D3):c.290C>T(p.Thr97Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,613,664 control chromosomes in the GnomAD database, including 8,294 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.057 ( 383 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7911 hom. )

Consequence

OR12D3
NM_030959.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

OR12D3 (HGNC:13963): (olfactory receptor family 12 subfamily D 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]

OR12D3 links:

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V member 1) 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]

OR5V1 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=0.003885895).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR12D3	NM_030959.3 link	c.290C>T	p.Thr97Ile	missense_variant	1/1	ENST00000396806.3	NP_112221.1	Q9UGF7D2XT27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR12D3	ENST00000396806.3 link	c.290C>T	p.Thr97Ile	missense_variant	1/1	6	NM_030959.3	ENSP00000380023.3		Q9UGF7
OR5V1	ENST00000377154.1 link	c.-82-18721C>T		intron_variant		6		ENSP00000366359.1		Q9UGF6

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8669

AN:

152086

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0445

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0945

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0548

AC:

13520

AN:

246924

Hom.:

559

AF XY:

0.0556

AC XY:

7478

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0377

Gnomad EAS exome

AF:

0.0133

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0446

Gnomad NFE exome

AF:

0.0916

Gnomad OTH exome

AF:

0.0536

GnomAD4 exome

AF:

0.0953

AC:

139284

AN:

1461460

Hom.:

7911

Cov.:

AF XY:

0.0925

AC XY:

67280

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0389

Gnomad4 EAS exome

AF:

0.0506

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0463

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0569

AC:

8667

AN:

152204

Hom.:

383

Cov.:

AF XY:

0.0517

AC XY:

3844

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.0262

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.0286

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.0445

Gnomad4 NFE

AF:

0.0945

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0848

Hom.:

1364

Bravo

AF:

0.0538

TwinsUK

AF:

0.133

AC:

493

ALSPAC

AF:

0.119

AC:

459

ESP6500AA

AF:

0.0235

AC:

ESP6500EA

AF:

0.0951

AC:

515

ExAC

AF:

0.0538

AC:

6452

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0901

EpiControl

AF:

0.0853

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.7

DANN

Benign

0.90

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.021

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.052

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.022

Vest4

0.051

MPC

0.19

ClinPred

0.00055

GERP RS

2.3

Varity_R

0.063

gMVP

0.046

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