11-59515162-G-T

Variant names:

• chr11-59515162-G-T
• rs757121618
• NM_001004711.2:c.250G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004711.2(OR4D9):​c.250G>T​(p.Asp84Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR4D9 NM_001004711.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

Genes affected

OR4D9 (HGNC:15178): (olfactory receptor family 4 subfamily D member 9) 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D9	NM_001004711.2	c.250G>T	p.Asp84Tyr	missense_variant	Exon 3 of 3	ENST00000641962.1	NP_001004711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D9	ENST00000641962.1	c.250G>T	p.Asp84Tyr	missense_variant	Exon 3 of 3		NM_001004711.2	ENSP00000493010.1
OR4D9	ENST00000641278.1	c.250G>T	p.Asp84Tyr	missense_variant	Exon 3 of 3			ENSP00000493042.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251306 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135814

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.86	.;.;D
M_CAP	Benign	0.0031	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.2	M;M;M
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-7.6	.;.;D
REVEL	Benign	0.087
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0050	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.49
MutPred		0.58		Loss of ubiquitination at K80 (P = 0.0795);Loss of ubiquitination at K80 (P = 0.0795);Loss of ubiquitination at K80 (P = 0.0795);
MVP		0.55
MPC		0.21
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.76
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs757121618; hg19: chr11-59282635;