9-122526483-C-A

Position:

• chr9-122526483-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012363.1(OR1N1):​c.811G>T​(p.Ala271Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR1N1 NM_012363.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.88

Genes affected

OR1N1 (HGNC:8221): (olfactory receptor family 1 subfamily N 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]

ENSG00000234156 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15248665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1N1	NM_012363.1	c.811G>T	p.Ala271Ser	missense_variant	1/1	ENST00000304880.2	NP_036495.1
OR1J2	XR_007061271.1	n.1540+23613C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1N1	ENST00000304880.2	c.811G>T	p.Ala271Ser	missense_variant	1/1	6	NM_012363.1	ENSP00000306974.2
ENSG00000234156	ENST00000431442.2	n.1362+23613C>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702676

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.811G>T (p.A271S) alteration is located in exon 1 (coding exon 1) of the OR1N1 gene. This alteration results from a G to T substitution at nucleotide position 811, causing the alanine (A) at amino acid position 271 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	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.097
Sift	Uncertain	0.022	D;.
Sift4G	Uncertain	0.053	T;T
Polyphen		0.97	D;.
Vest4		0.093
MutPred		0.56		Gain of glycosylation at A271 (P = 0.0301);.;
MVP		0.20
MPC		0.14
ClinPred		0.76	D
GERP RS		-1.0
Varity_R		0.26
gMVP		0.037

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-125288762;