NM_001004691.1:c.881A>T

Variant names:

• chr1-248323688-T-A
• rs374933101
• NM_001004691.1:c.881A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001004691.1(OR2M7):​c.881A>T​(p.Asn294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,611,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N294S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: OR2M7 NM_001004691.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.785
• Publications: 1 publications found

Genes affected

OR2M7 (HGNC:19594): (olfactory receptor family 2 subfamily M member 7) 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.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004691.1. 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
	OR2M7	NM_001004691.1	MANE Select	c.881A>T	p.Asn294Ile	missense	Exon 1 of 1	NP_001004691.1	Q8NG81

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M7	ENST00000317965.3	TSL:6 MANE Select	c.881A>T	p.Asn294Ile	missense	Exon 1 of 1	ENSP00000324557.2	Q8NG81

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000403 AC: 10 AN: 248234 AF XY: 0.0000298

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: 0.0000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 189 AN: 1459052 Hom.: 0 Cov.: 33 AF XY: 0.000130 AC XY: 94 AN XY: 725688

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1110618

Other (OTH) AF: 0.000299 AC: 18 AN: 60234

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.42	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0022	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		0.79
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.62
MVP		0.68
MPC		0.23
ClinPred		0.97	D
GERP RS		1.6
Varity_R		0.85
gMVP		0.16
Mutation Taster		=99/1	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: rs374933101; hg19: chr1-248486990;