1-248473637-C-T

Variant names:

• chr1-248473637-C-T
• rs749274432
• NM_001005495.1:c.287C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005495.1(OR2T3):​c.287C>T​(p.Thr96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000062 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T3 NM_001005495.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16668692).

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.287C>T	p.Thr96Ile	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.287C>T	p.Thr96Ile	missense	Exon 1 of 1	ENSP00000352604.2	Q8NH03

Frequencies

GnomAD3 genomes AF: 0.0000333 AC: 5 AN: 150238 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000799 AC: 2 AN: 250428 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460948 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 726828

African (AFR) AF: 0.00 AC: 0 AN: 33062

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111674

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000333 AC: 5 AN: 150348 Hom.: 0 Cov.: 26 AF XY: 0.0000545 AC XY: 4 AN XY: 73432

African (AFR) AF: 0.00 AC: 0 AN: 40396

American (AMR) AF: 0.000265 AC: 4 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67798

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.5
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.035
Sift	Benign	0.039	D
Sift4G	Benign	0.066	T
Polyphen		0.90	P
Vest4		0.060
MutPred		0.47		Loss of disorder (P = 0.0219)
MVP		0.33
ClinPred		0.33	T
GERP RS		2.3
PromoterAI		0.078	Neutral
Varity_R		0.13
gMVP		0.036
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs749274432; hg19: chr1-248636938; COSMIC: COSV100613459;