chr1-248295193-C-T

Variant names:

• chr1-248295193-C-T
• rs1313684942
• NM_001004692.2:c.386G>A

Variant summary

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

The NM_001004692.2(OR2T12):​c.386G>A​(p.Arg129Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,609,258 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: OR2T12 NM_001004692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.25
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14628834).

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.386G>A	p.Arg129Gln	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.386G>A	p.Arg129Gln	missense	Exon 3 of 3	ENSP00000493000.1	Q8NG77

Frequencies

GnomAD3 genomes AF: 0.0000534 AC: 8 AN: 149836 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000667

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

GnomAD2 exomes AF: 0.00000880 AC: 2 AN: 227212 AF XY: 0.00000811

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459422 Hom.: 0 Cov.: 76 AF XY: 0.00000138 AC XY: 1 AN XY: 726016

African (AFR) AF: 0.000120 AC: 4 AN: 33388

American (AMR) AF: 0.0000224 AC: 1 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4140

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111604

Other (OTH) AF: 0.0000332 AC: 2 AN: 60192

GnomAD4 genome AF: 0.0000534 AC: 8 AN: 149836 Hom.: 0 Cov.: 26 AF XY: 0.0000411 AC XY: 3 AN XY: 73002

African (AFR) AF: 0.000174 AC: 7 AN: 40164

American (AMR) AF: 0.0000667 AC: 1 AN: 14996

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2038

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	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-2.3
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.055
Sift	Benign	0.11	T
Sift4G	Benign	0.16	T
Polyphen		0.85	P
Vest4		0.065
MutPred		0.59		Loss of methylation at R129 (P = 0.1291)
MVP		0.32
MPC		0.73
ClinPred		0.42	T
GERP RS		0.32
Varity_R		0.092
gMVP		0.14
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1313684942; hg19: chr1-248458495; COSMIC: COSV100527963;