11-56137264-C-A

Variant names:

• chr11-56137264-C-A
• NM_001004064.2:c.455G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004064.2(OR8J3):​c.455G>T​(p.Gly152Val) 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. 13/22 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)
• Consequence: OR8J3 NM_001004064.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0180
• Publications: 0 publications found

Genes affected

OR8J3 (HGNC:15312): (olfactory receptor family 8 subfamily J member 3) Predicted to enable odorant binding activity and olfactory receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of smell. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28468567).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004064.2. 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
	OR8J3	NM_001004064.2	MANE Select	c.455G>T	p.Gly152Val	missense	Exon 2 of 2	NP_001004064.1	A0A126GVE3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8J3	ENST00000642058.1	MANE Select	c.455G>T	p.Gly152Val	missense	Exon 2 of 2	ENSP00000493166.1	Q8NGG0
	OR8J3	ENST00000641913.1		c.455G>T	p.Gly152Val	missense	Exon 2 of 2	ENSP00000493417.1	Q8NGG0
	OR8J3	ENST00000641489.1		n.30-226G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.0060
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.018
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.93	P
Vest4		0.25
MutPred		0.61		Gain of helix (P = 0.1736)
MVP		0.59
MPC		0.053
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.46
gMVP		0.38
Mutation Taster		=99/1	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

hg19: chr11-55904740; COSMIC: COSV56881602; COSMIC: COSV56881602;