1-248473460-T-A

Position:

• chr1-248473460-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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. 13/20 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

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

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=0.01373595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T3	NM_001005495.1	c.110T>A	p.Phe37Tyr	missense_variant	1/1	ENST00000359594.3
LOC105373279	XR_007067006.1	n.136-3301A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T3	ENST00000359594.3	c.110T>A	p.Phe37Tyr	missense_variant	1/1		NM_001005495.1	P1

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

GnomAD3 exomes AF: 0.000224 AC: 51 AN: 228026 Hom.: 0 AF XY: 0.000196 AC XY: 24 AN XY: 122666

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.00168

Gnomad4 AMR exome AF: 0.000342

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000415

Gnomad4 OTH exome AF: 0.000124

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

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000413

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.000517

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.110T>A (p.F37Y) alteration is located in exon 1 (coding exon 1) of the OR2T3 gene. This alteration results from a T to A substitution at nucleotide position 110, causing the phenylalanine (F) at amino acid position 37 to be replaced by a tyrosine (Y). 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	0.24
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
MutationTaster	Benign	1.0	N
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
Varity_R		0.34
gMVP		0.070

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: rs140073479; hg19: chr1-248636761;