NM_001004719.2:c.131T>C

Variant names:

• chr15-22080755-T-C
• rs148553963
• NM_001004719.2:c.131T>C

Variant summary

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

The NM_001004719.2(OR4M2):​c.131T>C​(p.Leu44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. L44R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: OR4M2 NM_001004719.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4M2	NM_001004719.2	c.131T>C	p.Leu44Pro	missense_variant	Exon 1 of 1	ENST00000614722.3	NP_001004719.2
OR4M2-OT1	NR_110480.2	n.824-13758T>C		intron_variant	Intron 7 of 8
OR4M2-OT1	NR_110481.2	n.556-13758T>C		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4M2	ENST00000614722.3	c.131T>C	p.Leu44Pro	missense_variant	Exon 1 of 1	6	NM_001004719.2	ENSP00000483239.1
OR4M2-OT1	ENST00000639059.1	c.-9-13758T>C		intron_variant	Intron 6 of 6	2		ENSP00000493899.1
OR4M2	ENST00000638815.1	n.268-102T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251374 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.070
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		0.34
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.72		Loss of stability (P = 0.0875);
MVP		0.62
ClinPred		0.98	D
GERP RS		2.5
PromoterAI		-0.0040	Neutral
Varity_R		0.84
gMVP		0.53

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: rs148553963; hg19: chr15-22368706;