NM_001001964.2:c.785T>G

Variant names:

• chr1-248626344-A-C
• rs749203508
• NM_001001964.2:c.785T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001964.2(OR2T11):​c.785T>G​(p.Phe262Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,573,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: OR2T11 NM_001001964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.196
• Publications: 1 publications found

Genes affected

OR2T11 (HGNC:19574): (olfactory receptor family 2 subfamily T member 11) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ENSG00000229255 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03631246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001964.2. 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
	OR2T11	NM_001001964.2	MANE Select	c.785T>G	p.Phe262Cys	missense	Exon 2 of 2	NP_001001964.1	Q8NH01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T11	ENST00000641193.1	MANE Select	c.785T>G	p.Phe262Cys	missense	Exon 2 of 2	ENSP00000492951.1	Q8NH01
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+16322T>G		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+16322T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000489 AC: 7 AN: 143230 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00121

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000735 AC: 18 AN: 244782 AF XY: 0.0000528

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000979 AC: 14 AN: 1430110 Hom.: 0 Cov.: 37 AF XY: 0.00000703 AC XY: 5 AN XY: 711684

African (AFR) AF: 0.00 AC: 0 AN: 30716

American (AMR) AF: 0.00 AC: 0 AN: 43682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25744

East Asian (EAS) AF: 0.000362 AC: 14 AN: 38708

South Asian (SAS) AF: 0.00 AC: 0 AN: 84376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090518

Other (OTH) AF: 0.00 AC: 0 AN: 59166

GnomAD4 genome AF: 0.0000489 AC: 7 AN: 143230 Hom.: 0 Cov.: 28 AF XY: 0.0000717 AC XY: 5 AN XY: 69774

African (AFR) AF: 0.00 AC: 0 AN: 36302

American (AMR) AF: 0.00 AC: 0 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00121 AC: 6 AN: 4966

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66224

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000674 AC: 8

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	0.16
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.20
PrimateAI	Benign	0.28	T
Polyphen		0.99	D
MutPred		0.28		Gain of catalytic residue at T264 (P = 0.0901)
ClinPred		0.40	T
GERP RS		1.7
Varity_R		0.13
gMVP		0.10
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: rs749203508; hg19: chr1-248789645;