rs762738891

Variant names:

• chr1-248473564-G-A
• rs762738891
• NM_001005495.1:c.214G>A

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.214G>A​(p.Ala72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 147,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T3 NM_001005495.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.225
• Publications: 6 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=0.07177383).

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.214G>A	p.Ala72Thr	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.214G>A	p.Ala72Thr	missense	Exon 1 of 1	ENSP00000352604.2	Q8NH03

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 147188 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000894 AC: 2 AN: 223762 AF XY: 0.00000829

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: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000260 AC: 37 AN: 1420380 Hom.: 0 Cov.: 27 AF XY: 0.0000226 AC XY: 16 AN XY: 708660

African (AFR) AF: 0.00 AC: 0 AN: 32162

American (AMR) AF: 0.0000225 AC: 1 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.0000288 AC: 31 AN: 1075568

Other (OTH) AF: 0.0000339 AC: 2 AN: 58990

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 147188 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 71420

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

African (AFR) AF: 0.0000502 AC: 2 AN: 39804

American (AMR) AF: 0.00 AC: 0 AN: 14472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 4922

South Asian (SAS) AF: 0.00 AC: 0 AN: 4388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66824

Other (OTH) AF: 0.00 AC: 0 AN: 2000

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000945577), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000829 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	0.26
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.23
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.058
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.27	B
Vest4		0.10
MutPred		0.59		Loss of stability (P = 0.0612)
MVP		0.19
ClinPred		0.081	T
GERP RS		-3.6
PromoterAI		0.00090	Neutral
Varity_R		0.11
gMVP		0.054
Mutation Taster		=100/0	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: rs762738891; hg19: chr1-248636865; COSMIC: COSV62083659;