11-56137388-C-G

Variant names:

• chr11-56137388-C-G
• NM_001004064.2:c.331G>C

Variant summary

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

The NM_001004064.2(OR8J3):​c.331G>C​(p.Glu111Gln) 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. 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: 0.642

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 rank	MANE	Protein	UniProt
OR8J3	NM_001004064.2	c.331G>C	p.Glu111Gln	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.331G>C	p.Glu111Gln	missense_variant	Exon 2 of 2		NM_001004064.2	ENSP00000493166.1
OR8J3	ENST00000641913.1	c.331G>C	p.Glu111Gln	missense_variant	Exon 2 of 2			ENSP00000493417.1
OR8J3	ENST00000641489.1	n.30-350G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.331G>C (p.E111Q) alteration is located in exon 1 (coding exon 1) of the OR8J3 gene. This alteration results from a G to C substitution at nucleotide position 331, causing the glutamic acid (E) at amino acid position 111 to be replaced by a glutamine (Q). 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	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0058	T;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.77	.;.;T
M_CAP	Benign	0.00060	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.9	.;.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	.;.;D
Sift4G	Pathogenic	0.0010	.;.;D
Polyphen		0.98	D;D;D
Vest4		0.22
MutPred		0.44		Gain of helix (P = 0.5668);Gain of helix (P = 0.5668);Gain of helix (P = 0.5668);
MVP		0.38
MPC		0.059
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.76
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -3

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: chr11-55904864;