rs139107079

Variant names:

• chr1-248203330-G-T
• rs139107079
• NM_001004689.2:c.263G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-248203330-G-T
• chr1-248203330-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004689.2(OR2M3):​c.263G>T​(p.Gly88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 1,614,016 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00047 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00087 (3 hom.)
• Consequence: OR2M3 NM_001004689.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.30
• Publications: 2 publications found

Genes affected

OR2M3 (HGNC:8269): (olfactory receptor family 2 subfamily M member 3) 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032205105).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004689.2. 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
	OR2M3	NM_001004689.2	MANE Select	c.263G>T	p.Gly88Val	missense	Exon 2 of 2	NP_001004689.1	Q8NG83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M3	ENST00000641626.1	MANE Select	c.263G>T	p.Gly88Val	missense	Exon 2 of 2	ENSP00000492981.1	Q8NG83
	OR2M3	ENST00000456743.3	TSL:6	c.263G>T	p.Gly88Val	missense	Exon 1 of 1	ENSP00000389625.1	Q8NG83

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 152030 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000493 AC: 124 AN: 251398 AF XY: 0.000559

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000915

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000868 AC: 1269 AN: 1461868 Hom.: 3 Cov.: 30 AF XY: 0.000851 AC XY: 619 AN XY: 727238

African (AFR) AF: 0.000149 AC: 5 AN: 33474

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26136

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

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00106 AC: 1179 AN: 1111998

Other (OTH) AF: 0.000729 AC: 44 AN: 60394

GnomAD4 genome AF: 0.000467 AC: 71 AN: 152148 Hom.: 0 Cov.: 31 AF XY: 0.000484 AC XY: 36 AN XY: 74350

African (AFR) AF: 0.000217 AC: 9 AN: 41510

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68002

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000853 Hom.: 0

Bravo AF: 0.000476

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000428 AC: 52

EpiCase AF: 0.00104

EpiControl AF: 0.00107

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	0.26
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-1.3
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.025
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.93	P
Vest4		0.13
MVP		0.40
MPC		0.19
ClinPred		0.073	T
GERP RS		0.33
PromoterAI		0.0055	Neutral
Varity_R		0.29
gMVP		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139107079; hg19: chr1-248366632;