rs1372315216

Variant names:

• chr1-248473571-T-A
• rs1372315216
• NM_001005495.1:c.221T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-248473571-T-A
• chr1-248473571-T-C

Variant summary

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

The NM_001005495.1(OR2T3):​c.221T>A​(p.Met74Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M74T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: OR2T3 NM_001005495.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.221T>A	p.Met74Lys	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.221T>A	p.Met74Lys	missense	Exon 1 of 1	ENSP00000352604.2	Q8NH03

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0010	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.93
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.51
MutPred		0.62		Loss of stability (P = 0.0123)
MVP		0.49
ClinPred		0.76	D
GERP RS		1.5
PromoterAI		0.014	Neutral
Varity_R		0.92
gMVP		0.41
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: rs1372315216; hg19: chr1-248636872;