1-248626738-C-A

Variant names:

• chr1-248626738-C-A
• rs765476981
• NM_001001964.2:c.391G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001964.2(OR2T11):​c.391G>T​(p.Val131Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,430,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000035 (1 hom.)
• Consequence: OR2T11 NM_001001964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.09
• Publications: 2 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: 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=0.20997125).

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.391G>T	p.Val131Phe	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.391G>T	p.Val131Phe	missense	Exon 2 of 2	ENSP00000492951.1	Q8NH01
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+15928G>T		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+15928G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244558 AF XY: 0.00000755

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: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1430508 Hom.: 1 Cov.: 38 AF XY: 0.00000421 AC XY: 3 AN XY: 711852

African (AFR) AF: 0.00 AC: 0 AN: 30724

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 38720

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000458 AC: 5 AN: 1090862

Other (OTH) AF: 0.00 AC: 0 AN: 59200

GnomAD4 genome Cov.: 28

Alfa AF: 0.0000380 Hom.: 0

ExAC AF: 0.00000842 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000603

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	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-3.1
PrimateAI	Benign	0.40	T
Polyphen		0.012	B
ClinPred		0.78	D
GERP RS		3.5
Varity_R		0.33
gMVP		0.21
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: rs765476981; hg19: chr1-248790039;