rs3749971

chr6-29374998-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.057 (383 hom., cov: 32)
  • Exomes 𝑓: 0.095 (7911 hom.)
• Consequence: OR12D3 NM_030959.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

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]

ACMG classification

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	UniProt
OR12D3	NM_030959.3	c.290C>T	p.Thr97Ile	missense_variant	1/1	ENST00000396806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR12D3	ENST00000396806.3	c.290C>T	p.Thr97Ile	missense_variant	1/1		NM_030959.3	P1
OR5V1	ENST00000377154.1	c.-82-18721C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8669 AN: 152086 Hom.: 383 Cov.: 32

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

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.: 35 AF XY: 0.0925 AC XY: 67280 AN XY: 727056

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.: 32 AF XY: 0.0517 AC XY: 3844 AN XY: 74418

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: 71

ESP6500EA AF: 0.0951 AC: 515

ExAC AF: 0.0538 AC: 6452

Asia WGS AF: 0.0200 AC: 70 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	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.7
Dann	Benign	0.90
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.021	N
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.052
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.022	B
Vest4		0.051
MPC		0.19
ClinPred		0.00055	T
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

Other links and lift over

dbSNP: rs3749971; hg19: chr6-29342775;