11-56137230-T-C

Position:

• chr11-56137230-T-C

Variant summary

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

The NM_001004064.2(OR8J3):​c.489A>G​(p.Ile163Met) 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. 13/23 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: -3.93

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8J3	NM_001004064.2	c.489A>G	p.Ile163Met	missense_variant	2/2	ENST00000642058.1	NP_001004064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8J3	ENST00000642058.1	c.489A>G	p.Ile163Met	missense_variant	2/2		NM_001004064.2	ENSP00000493166.1
OR8J3	ENST00000641913.1	c.489A>G	p.Ile163Met	missense_variant	2/2			ENSP00000493417.1
OR8J3	ENST00000641489.1	n.30-192A>G		intron_variant

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.489A>G (p.I163M) alteration is located in exon 1 (coding exon 1) of the OR8J3 gene. This alteration results from a A to G substitution at nucleotide position 489, causing the isoleucine (I) at amino acid position 163 to be replaced by a methionine (M). 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	0.17
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0052	T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.49	.;.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.96	L;L;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.9	.;.;N
REVEL	Benign	0.076
Sift	Benign	0.030	.;.;D
Sift4G	Benign	0.51	.;.;T
Polyphen		0.59	P;P;P
Vest4		0.036
MutPred		0.23		Loss of stability (P = 0.1048);Loss of stability (P = 0.1048);Loss of stability (P = 0.1048);
MVP		0.11
MPC		0.030
ClinPred		0.37	T
GERP RS		3.3
Varity_R		0.15
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 5

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: chr11-55904706;