7-143026288-T-A

Variant names:

• chr7-143026288-T-A
• rs148601591
• NM_001001658.1:c.845A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001001658.1(OR9A2):​c.845A>T​(p.Asn282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: OR9A2 NM_001001658.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 6 publications found

Genes affected

OR9A2 (HGNC:15093): (olfactory receptor family 9 subfamily A member 2) 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 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001658.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR9A2	NM_001001658.1	MANE Select	c.845A>T	p.Asn282Ile	missense	Exon 1 of 1	NP_001001658.1	Q8NGT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR9A2	ENST00000350513.3	TSL:6 MANE Select	c.845A>T	p.Asn282Ile	missense	Exon 1 of 1	ENSP00000316518.3	Q8NGT5

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 151966 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000255 AC: 64 AN: 251356 AF XY: 0.000309

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000296 AC: 432 AN: 1461814 Hom.: 0 Cov.: 32 AF XY: 0.000303 AC XY: 220 AN XY: 727206

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000376 AC: 418 AN: 1111974

Other (OTH) AF: 0.000149 AC: 9 AN: 60392

GnomAD4 genome AF: 0.000296 AC: 45 AN: 151966 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74210

African (AFR) AF: 0.0000967 AC: 4 AN: 41366

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000354 Hom.: 0

Bravo AF: 0.000227

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	4.6	H
PhyloP100		3.1
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.66
MVP		0.85
MPC		0.77
ClinPred		0.43	T
GERP RS		1.8
Varity_R		0.28
gMVP		0.80
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs148601591; hg19: chr7-142723375; COSMIC: COSV106108246;