9-122662479-T-G

Variant names:

• chr9-122662479-T-G
• rs1830526835
• NM_001005236.3:c.764T>G

Variant summary

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

The NM_001005236.3(OR1L1):​c.764T>G​(p.Ile255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OR1L1 NM_001005236.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.923

Genes affected

OR1L1 (HGNC:8213): (olfactory receptor family 1 subfamily L member 1) 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
OR1L1	NM_001005236.3	c.764T>G	p.Ile255Ser	missense_variant	Exon 1 of 1	ENST00000309623.1	NP_001005236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1L1	ENST00000309623.1	c.764T>G	p.Ile255Ser	missense_variant	Exon 1 of 1	6	NM_001005236.3	ENSP00000310773.1
OR1L1	ENST00000373686.1	c.914T>G	p.Ile305Ser	missense_variant	Exon 1 of 1	6		ENSP00000362790.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.764T>G (p.I255S) alteration is located in exon 1 (coding exon 1) of the OR1L1 gene. This alteration results from a T to G substitution at nucleotide position 764, causing the isoleucine (I) at amino acid position 255 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.079
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.045	D;T
Polyphen		0.99	D;.
Vest4		0.51
MutPred		0.65		Gain of sheet (P = 0.0344);.;
MVP		0.60
MPC		0.24
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.35
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1830526835; hg19: chr9-125424758;