NM_001004719.2:c.415C>T

Variant names:

Variant summary

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

The NM_001004719.2(OR4M2):c.415C>T(p.Arg139Cys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000027 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR4M2
NM_001004719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Publications

3 publications found

Variant links:

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 links:

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

OR4M2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.10608515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4M2	NM_001004719.2 link	c.415C>T	p.Arg139Cys	missense_variant	Exon 1 of 1	ENST00000614722.3	NP_001004719.2	Q8NGB6
OR4M2-OT1	NR_110480.2 link	n.824-13474C>T		intron_variant	Intron 7 of 8
OR4M2-OT1	NR_110481.2 link	n.556-13474C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR4M2	ENST00000614722.3 link	c.415C>T	p.Arg139Cys	missense_variant	Exon 1 of 1	6	NM_001004719.2	ENSP00000483239.1	Q8NGB6
OR4M2-OT1	ENST00000639059.1 link	c.-9-13474C>T		intron_variant	Intron 6 of 6	2		ENSP00000493899.1
OR4M2	ENST00000638815.1 link	n.450C>T		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251348

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000273

AC:

AN:

73202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

39076

show subpopulations

African (AFR)

AF:

0.000369

AC:

AN:

5416

American (AMR)

AF:

0.00

AC:

AN:

2674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2172

East Asian (EAS)

AF:

0.00

AC:

AN:

2410

South Asian (SAS)

AF:

0.00

AC:

AN:

10678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

484

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

40698

Other (OTH)

AF:

0.00

AC:

AN:

4986

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.415C>T (p.R139C) alteration is located in exon 1 (coding exon 1) of the OR4M2 gene. This alteration results from a C to T substitution at nucleotide position 415, causing the arginine (R) at amino acid position 139 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.59

M_CAP

Benign

0.0048

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

PhyloP100

-1.1

Sift4G

Uncertain

0.0050

Polyphen

0.019

Vest4

0.21

MutPred

0.44

Gain of catalytic residue at C142 (P = 0.1237);

MVP

0.30

ClinPred

0.27

GERP RS

0.48

Varity_R

0.15

gMVP

0.31

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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NM_001004719.2:c.415C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over