NM_001004691.1:c.653A>G

Variant names:

• chr1-248323916-T-C
• rs1444665060
• NM_001004691.1:c.653A>G

Variant summary

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

The NM_001004691.1(OR2M7):​c.653A>G​(p.Tyr218Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR2M7 NM_001004691.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• 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 2 ACMG points.

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

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.653A>G	p.Tyr218Cys	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.653A>G	p.Tyr218Cys	missense	Exon 1 of 1	ENSP00000324557.2	Q8NG81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251076 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460810 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 726758

⚠️ 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: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5074

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111812

Other (OTH) AF: 0.0000166 AC: 1 AN: 60294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.00052	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		6.0
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Benign	0.095
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.030	D
Polyphen		0.53	P
Vest4		0.44
MutPred		0.72		Loss of glycosylation at T216 (P = 0.0444)
MVP		0.31
MPC		0.19
ClinPred		0.99	D
GERP RS		1.6
Varity_R		0.65
gMVP		0.22
Mutation Taster		=87/13	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: rs1444665060; hg19: chr1-248487218;