NM_001004692.2:c.872G>A

Variant names:

• chr1-248294707-C-T
• rs1271800604
• NM_001004692.2:c.872G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004692.2(OR2T12):​c.872G>A​(p.Arg291Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OR2T12 NM_001004692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0360
• Publications: 1 publications found

Genes affected

OR2T12 (HGNC:19592): (olfactory receptor family 2 subfamily T member 12) 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41449597).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004692.2. 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
	OR2T12	NM_001004692.2	MANE Select	c.872G>A	p.Arg291Lys	missense	Exon 3 of 3	NP_001004692.1	Q8NG77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T12	ENST00000641276.1	MANE Select	c.872G>A	p.Arg291Lys	missense	Exon 3 of 3	ENSP00000493000.1	Q8NG77

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152080 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000242

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251484 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461852 Hom.: 0 Cov.: 102 AF XY: 0.0000193 AC XY: 14 AN XY: 727226

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111978

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000181092), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152080 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74268

African (AFR) AF: 0.0000242 AC: 1 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000122 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	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.036
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.076
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.036	D
Polyphen		0.012	B
Vest4		0.17
MutPred		0.77		Gain of methylation at R291 (P = 0.0059)
MVP		0.38
MPC		0.48
ClinPred		0.29	T
GERP RS		1.7
Varity_R		0.21
gMVP		0.22
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1271800604; hg19: chr1-248458009;