ENST00000641504.1:c.209A>T

Variant names:

• chr11-75089505-T-A
• rs762495764
• NM_001405852.1:c.209A>T

Variant summary

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

The ENST00000641504.1(OR2AT4):​c.209A>T​(p.Asn70Ile) 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. N70S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2AT4 ENST00000641504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 1 publications found

Genes affected

OR2AT4 (HGNC:19620): (olfactory receptor family 2 subfamily AT member 4) 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]

ENSG00000284722 (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: ENST00000641504.1. 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
	OR2AT4	NM_001405852.1	MANE Select	c.209A>T	p.Asn70Ile	missense	Exon 2 of 2	NP_001392781.1	A0A126GWB1
	OR2AT4	NM_001005285.2		c.209A>T	p.Asn70Ile	missense	Exon 2 of 2	NP_001005285.1	A6NND4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AT4	ENST00000641504.1	MANE Select	c.209A>T	p.Asn70Ile	missense	Exon 2 of 2	ENSP00000493318.1	A6NND4
	OR2AT4	ENST00000305159.3	TSL:6	c.209A>T	p.Asn70Ile	missense	Exon 1 of 1	ENSP00000304846.3	A6NND4
	OR2AT4	ENST00000641541.1		c.209A>T	p.Asn70Ile	missense	Exon 3 of 3	ENSP00000493299.1	A6NND4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.26
Sift	Benign	0.054	T
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.52		Loss of catalytic residue at N70 (P = 0.0016)
MVP		0.38
MPC		0.27
ClinPred		0.97	D
GERP RS		5.0
PromoterAI		0.0038	Neutral
Varity_R		0.56
gMVP		0.55
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs762495764; hg19: chr11-74800550;