11-4594444-T-C

Variant names:

• chr11-4594444-T-C
• rs1400318945
• NM_001005169.1:c.406T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005169.1(OR52I1):​c.406T>C​(p.Tyr136His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR52I1 NM_001005169.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

Genes affected

OR52I1 (HGNC:15220): (olfactory receptor family 52 subfamily I 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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005169.1. 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
	OR52I1	NM_001005169.1	MANE Select	c.406T>C	p.Tyr136His	missense	Exon 1 of 1	NP_001005169.1	Q8NGK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52I1	ENST00000530443.4	TSL:6 MANE Select	c.406T>C	p.Tyr136His	missense	Exon 1 of 1	ENSP00000436453.1	Q8NGK6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251328 AF XY: 0.00

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 FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461878 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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	0.17
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0095	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.9
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Polyphen		0.66	P
Vest4		0.33
MutPred		0.72		Loss of catalytic residue at Y136 (P = 0.1286)
MVP		0.73
MPC		1.0
ClinPred		0.70	D
GERP RS		5.0
PromoterAI		-0.016	Neutral
Varity_R		0.39
gMVP		0.46
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1400318945; hg19: chr11-4615674; COSMIC: COSV56167634; COSMIC: COSV56167634;