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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8J3	NM_001004064.2	c.455G>T	p.Gly152Val	missense_variant	Exon 2 of 2	ENST00000642058.1	NP_001004064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8J3	ENST00000642058.1	c.455G>T	p.Gly152Val	missense_variant	Exon 2 of 2		NM_001004064.2	ENSP00000493166.1
OR8J3	ENST00000641913.1	c.455G>T	p.Gly152Val	missense_variant	Exon 2 of 2			ENSP00000493417.1
OR8J3	ENST00000641489.1	n.30-226G>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.455G>T (p.G152V) alteration is located in exon 1 (coding exon 1) of the OR8J3 gene. This alteration results from a G to T substitution at nucleotide position 455, causing the glycine (G) at amino acid position 152 to be replaced by a valine (V). 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	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T;T;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;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M;M;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;P;P
Vest4		0.25
MutPred		0.61		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);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;