NM_001001827.2:c.831C>G

Variant names:

• chr1-248638428-G-C
• rs1255070466
• NM_001001827.2:c.831C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001001827.2(OR2T35):​c.831C>G​(p.Phe277Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F277C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0400
• Publications: 0 publications found

Genes affected

OR2T35 (HGNC:31257): (olfactory receptor family 2 subfamily T member 35) 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]

ENSG00000229255 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26877725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001827.2. 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
	OR2T35	NM_001001827.2	MANE Select	c.831C>G	p.Phe277Leu	missense	Exon 2 of 2	NP_001001827.1	Q8NGX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T35	ENST00000641268.1	MANE Select	c.831C>G	p.Phe277Leu	missense	Exon 2 of 2	ENSP00000492995.1	Q8NGX2
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+4238C>G		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+4238C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000842 AC: 1 AN: 118734 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.0000314

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000122 AC: 14 AN: 1145282 Hom.: 0 Cov.: 17 AF XY: 0.0000120 AC XY: 7 AN XY: 583278

African (AFR) AF: 0.000175 AC: 5 AN: 28498

American (AMR) AF: 0.00 AC: 0 AN: 43460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23962

East Asian (EAS) AF: 0.00 AC: 0 AN: 38616

South Asian (SAS) AF: 0.00 AC: 0 AN: 81166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 822080

Other (OTH) AF: 0.000158 AC: 8 AN: 50586

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000168 AC: 2 AN: 118862 Hom.: 0 Cov.: 15 AF XY: 0.0000175 AC XY: 1 AN XY: 57070

African (AFR) AF: 0.0000626 AC: 2 AN: 31944

American (AMR) AF: 0.00 AC: 0 AN: 11732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2816

East Asian (EAS) AF: 0.00 AC: 0 AN: 3956

South Asian (SAS) AF: 0.00 AC: 0 AN: 3312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54934

Other (OTH) AF: 0.00 AC: 0 AN: 1454

Alfa AF: 0.0000843 Hom.: 0

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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.040
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.071
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.050	T
Polyphen		0.85	P
Vest4		0.26
MutPred		0.48		Loss of sheet (P = 0.1158)
MVP		0.56
MPC		1.9
ClinPred		0.94	D
GERP RS		1.0
Varity_R		0.54
gMVP		0.065
Mutation Taster		=91/9	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: rs1255070466; hg19: chr1-248801729;