NM_001004719.2:c.230C>T

Variant names:

• chr15-22080854-C-T
• rs1892882612
• NM_001004719.2:c.230C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004719.2(OR4M2):​c.230C>T​(p.Thr77Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OR4M2 NM_001004719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.751
• Publications: 0 publications found

Genes affected

OR4M2 (HGNC:15373): (olfactory receptor family 4 subfamily M member 2) 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]

OR4M2-OT1 (HGNC:56199): (OR4M2 overlapping transcript 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16997513).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004719.2. 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
	OR4M2	NM_001004719.2	MANE Select	c.230C>T	p.Thr77Ile	missense	Exon 1 of 1	NP_001004719.2	Q8NGB6
	OR4M2-OT1	NR_110480.2		n.824-13659C>T		intron	N/A
	OR4M2-OT1	NR_110481.2		n.556-13659C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4M2	ENST00000614722.3	TSL:6 MANE Select	c.230C>T	p.Thr77Ile	missense	Exon 1 of 1	ENSP00000483239.1	Q8NGB6
	OR4M2-OT1	ENST00000639059.1	TSL:2	c.-9-13659C>T		intron	N/A	ENSP00000493899.1
	OR4M2	ENST00000638815.1	TSL:5	n.268-3C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.75
Sift4G	Benign	0.085	T
Polyphen		0.90	P
Vest4		0.12
MutPred		0.30		Gain of catalytic residue at L82 (P = 0.0204)
MVP		0.56
ClinPred		0.97	D
GERP RS		2.5
PromoterAI		-0.012	Neutral
Varity_R		0.15
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1892882612; hg19: chr15-22368805;