1-248626563-G-C

Variant names:

• chr1-248626563-G-C
• rs779951510
• NM_001001964.2:c.566C>G

Variant summary

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

The NM_001001964.2(OR2T11):​c.566C>G​(p.Thr189Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. T189M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OR2T11 NM_001001964.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 0 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 2 ACMG points.

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

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.566C>G	p.Thr189Arg	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.566C>G	p.Thr189Arg	missense	Exon 2 of 2	ENSP00000492951.1	Q8NH01
	ENSG00000229255	ENST00000450847.2	TSL:2	n.195+16103C>G		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.242+16103C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428028 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 710802

African (AFR) AF: 0.00 AC: 0 AN: 30648

American (AMR) AF: 0.00 AC: 0 AN: 43696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 38710

South Asian (SAS) AF: 0.00 AC: 0 AN: 84344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51266

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

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1088826

Other (OTH) AF: 0.00 AC: 0 AN: 59118

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.57
PrimateAI	Benign	0.22	T
Polyphen		0.37	B
MutPred		0.57		Gain of helix (P = 0.132)
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.25
gMVP		0.36
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs779951510; hg19: chr1-248789864; COSMIC: COSV100424929;