1-248145857-C-G

Variant names:

• chr1-248145857-C-G
• rs41304157
• NM_001004690.1:c.710C>G

Variant summary

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

The NM_001004690.1(OR2M5):​c.710C>G​(p.Ala237Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A237S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR2M5 NM_001004690.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

OR2M5 (HGNC:19576): (olfactory receptor family 2 subfamily M member 5) 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2M5	NM_001004690.1	c.710C>G	p.Ala237Gly	missense_variant	Exon 1 of 1	ENST00000366476.1	NP_001004690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M5	ENST00000366476.1	c.710C>G	p.Ala237Gly	missense_variant	Exon 1 of 1	6	NM_001004690.1	ENSP00000355432.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461258 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726946

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86230

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T
Eigen	Uncertain	0.43
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0016	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		2.3
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.93	P
Vest4		0.37
MutPred		0.68		Loss of stability (P = 0.0469);
MVP		0.067
MPC		0.13
ClinPred		0.94	D
GERP RS		3.0
Varity_R		0.43
gMVP		0.048
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41304157; hg19: chr1-248309159;