NM_001004453.3:c.644T>G

Variant names:

• chr9-122750491-T-G
• rs10985760
• NM_001004453.3:c.644T>G

Variant summary

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

The NM_001004453.3(OR1L6):​c.644T>G​(p.Ile215Ser) variant causes a missense change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000075 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR1L6 NM_001004453.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 18 publications found

Genes affected

OR1L6 (HGNC:8218): (olfactory receptor family 1 subfamily L member 6) 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L6	NM_001004453.3	MANE Select	c.644T>G	p.Ile215Ser	missense	Exon 2 of 2	NP_001004453.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L6	ENST00000304720.3	TSL:6 MANE Select	c.644T>G	p.Ile215Ser	missense	Exon 2 of 2	ENSP00000304235.2
	OR1L6	ENST00000373684.1	TSL:6	c.752T>G	p.Ile251Ser	missense	Exon 1 of 1	ENSP00000362788.1

Frequencies

GnomAD3 genomes AF: 0.00000754 AC: 1 AN: 132690 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000800

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000105 AC: 2 AN: 190408 AF XY: 0.0000197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000674

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000350 AC: 3 AN: 856498 Hom.: 0 Cov.: 12 AF XY: 0.00000450 AC XY: 2 AN XY: 444366

African (AFR) AF: 0.00 AC: 0 AN: 24448

American (AMR) AF: 0.0000723 AC: 3 AN: 41484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20034

East Asian (EAS) AF: 0.00 AC: 0 AN: 36676

South Asian (SAS) AF: 0.00 AC: 0 AN: 67978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 572654

Other (OTH) AF: 0.00 AC: 0 AN: 40478

GnomAD4 genome AF: 0.00000754 AC: 1 AN: 132690 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 63178

African (AFR) AF: 0.00 AC: 0 AN: 36032

American (AMR) AF: 0.0000800 AC: 1 AN: 12504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3208

East Asian (EAS) AF: 0.00 AC: 0 AN: 4432

South Asian (SAS) AF: 0.00 AC: 0 AN: 3444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61542

Other (OTH) AF: 0.00 AC: 0 AN: 1696

Alfa AF: 0.00 Hom.: 17110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.8
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.62
MutPred		0.58		Loss of stability (P = 0.0236)
MVP		0.88
MPC		0.93
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.87
gMVP		0.45
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10985760; hg19: chr9-125512770;