11-59477460-G-C

Variant names:

• chr11-59477460-G-C
• rs763306729
• NM_001004705.2:c.31G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001004705.2(OR4D10):​c.31G>C​(p.Glu11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. E11K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR4D10 NM_001004705.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

Genes affected

OR4D10 (HGNC:15173): (olfactory receptor family 4 subfamily D member 10) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D10	NM_001004705.2	c.31G>C	p.Glu11Gln	missense_variant	Exon 3 of 3	ENST00000530162.2	NP_001004705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D10	ENST00000530162.2	c.31G>C	p.Glu11Gln	missense_variant	Exon 3 of 3	6	NM_001004705.2	ENSP00000436424.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.036
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0056	T
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.022	D
Polyphen		0.98	D
Vest4		0.56
MutPred		0.57		Loss of ubiquitination at K10 (P = 0.0709);
MVP		0.47
MPC		0.064
ClinPred		0.74	D
GERP RS		3.1
Varity_R		0.11
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs763306729; hg19: chr11-59244933;