Variant 15-22081332-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004719.2(OR4M2):c.708C>A(p.Asn236Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 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)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4M2
NM_001004719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.481

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:):

OR4M2-OT1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11719224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR4M2	NM_001004719.2 linkuse as main transcript	c.708C>A	p.Asn236Lys	missense_variant	1/1	ENST00000614722.3
OR4M2-OT1	NR_110480.1 linkuse as main transcript	n.824-13181C>A		intron_variant, non_coding_transcript_variant
OR4M2-OT1	NR_110481.1 linkuse as main transcript	n.556-13181C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4M2	ENST00000614722.3 linkuse as main transcript	c.708C>A	p.Asn236Lys	missense_variant	1/1		NM_001004719.2	P1
OR4M2	ENST00000638815.1 linkuse as main transcript	n.512+231C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000384

AC:

AN:

260124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

130956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000535

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.708C>A (p.N236K) alteration is located in exon 1 (coding exon 1) of the OR4M2 gene. This alteration results from a C to A substitution at nucleotide position 708, causing the asparagine (N) at amino acid position 236 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

DANN

Benign

0.90

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.035

M_CAP

Benign

0.0023

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

MutationTaster

Benign

1.0

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.084

MutPred

0.38

Gain of methylation at N236 (P = 0.0032);

MVP

0.21

ClinPred

0.95

GERP RS

-0.63

Varity_R

0.062

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over