chr15-22080671-G-A

Position:

• chr15-22080671-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001004719.2(OR4M2):​c.47G>A​(p.Gly16Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic 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: 2.54

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4M2	NM_001004719.2	c.47G>A	p.Gly16Asp	missense_variant	1/1	ENST00000614722.3
OR4M2-OT1	NR_110480.1	n.824-13842G>A		intron_variant, non_coding_transcript_variant
OR4M2-OT1	NR_110481.1	n.556-13842G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4M2	ENST00000614722.3	c.47G>A	p.Gly16Asp	missense_variant	1/1		NM_001004719.2	P1
OR4M2	ENST00000638815.1	n.267+23G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251008 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135688

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.0000936 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.47G>A (p.G16D) alteration is located in exon 1 (coding exon 1) of the OR4M2 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0060	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	M
MutationTaster	Benign	0.50	N
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.73		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.67
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.10
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs778129001; hg19: chr15-22368622;