11-56469779-C-T

Variant names:

• chr11-56469779-C-T
• NM_001004742.3:c.719G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004742.3(OR5M3):​c.719G>A​(p.Gly240Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR5M3 NM_001004742.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

Genes affected

OR5M3 (HGNC:14806): (olfactory receptor family 5 subfamily M member 3) 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]

ENSG00000284732 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36345744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5M3	NM_001004742.3	c.719G>A	p.Gly240Glu	missense_variant	Exon 2 of 2	ENST00000641993.1	NP_001004742.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5M3	ENST00000641993.1	c.719G>A	p.Gly240Glu	missense_variant	Exon 2 of 2		NM_001004742.3	ENSP00000493070.1
ENSG00000284732	ENST00000641310.1	c.144+575G>A		intron_variant	Intron 2 of 3			ENSP00000493052.1
ENSG00000284732	ENST00000641599.1	c.144+575G>A		intron_variant	Intron 2 of 2			ENSP00000493241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460546 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726630

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	0.064
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-6.6	.;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		0.89	P;P
Vest4		0.41
MutPred		0.64		Loss of catalytic residue at C239 (P = 0.0666);Loss of catalytic residue at C239 (P = 0.0666);
MVP		0.74
MPC		0.30
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.97
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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.

Other links and lift over

hg19: chr11-56237255;