1-248473460-T-A

Variant names:

• chr1-248473460-T-A
• rs140073479
• NM_001005495.1:c.110T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005495.1(OR2T3):​c.110T>A​(p.Phe37Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,494,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F37V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: OR2T3 NM_001005495.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.867
• Publications: 1 publications found

Genes affected

OR2T3 (HGNC:14727): (olfactory receptor family 2 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]

LOC105373279 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01373595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005495.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T3	NM_001005495.1	MANE Select	c.110T>A	p.Phe37Tyr	missense	Exon 1 of 1	NP_001005495.1	Q8NH03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T3	ENST00000359594.3	TSL:6 MANE Select	c.110T>A	p.Phe37Tyr	missense	Exon 1 of 1	ENSP00000352604.2	Q8NH03

Frequencies

GnomAD3 genomes AF: 0.000613 AC: 89 AN: 145174 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000412

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.000522

GnomAD2 exomes AF: 0.000224 AC: 51 AN: 228026 AF XY: 0.000196

Gnomad AFR exome AF: 0.00188

Gnomad AMR exome AF: 0.000459

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000300

Gnomad OTH exome AF: 0.000364

GnomAD4 exome AF: 0.0000889 AC: 120 AN: 1349208 Hom.: 0 Cov.: 24 AF XY: 0.0000741 AC XY: 50 AN XY: 674622

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00168 AC: 54 AN: 32058

American (AMR) AF: 0.000342 AC: 15 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24762

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39148

South Asian (SAS) AF: 0.00 AC: 0 AN: 83164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.0000415 AC: 42 AN: 1011110

Other (OTH) AF: 0.000124 AC: 7 AN: 56592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000619 AC: 90 AN: 145284 Hom.: 0 Cov.: 25 AF XY: 0.000582 AC XY: 41 AN XY: 70502

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00183 AC: 73 AN: 39784

American (AMR) AF: 0.000915 AC: 13 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3326

East Asian (EAS) AF: 0.000413 AC: 2 AN: 4838

South Asian (SAS) AF: 0.00 AC: 0 AN: 4124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65822

Other (OTH) AF: 0.000517 AC: 1 AN: 1936

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000432 Hom.: 0

ESP6500AA AF: 0.00160 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000216 AC: 26

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.87
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.071
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.020	D
Polyphen		0.98	D
Vest4		0.25
MVP		0.31
ClinPred		0.021	T
GERP RS		2.9
PromoterAI		-0.042	Neutral
Varity_R		0.34
gMVP		0.070
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs140073479; hg19: chr1-248636761;