Genetic Variant OR8J3:p.Ser314Thr (chr11-56136779-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004064.2(OR8J3):c.940T>A(p.Ser314Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000582 in 1,546,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000057 ( 1 hom. )

Consequence

OR8J3
NM_001004064.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.24

Publications

1 publications found

Variant links:

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]

OR8J3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038541257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8J3	NM_001004064.2 link	c.940T>A	p.Ser314Thr	missense_variant	Exon 2 of 2	ENST00000642058.1	NP_001004064.1	Q8NGG0A0A126GVE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8J3	ENST00000642058.1 link	c.940T>A	p.Ser314Thr	missense_variant	Exon 2 of 2	NM_001004064.2	ENSP00000493166.1	Q8NGG0
OR8J3	ENST00000641913.1 link	c.940T>A	p.Ser314Thr	missense_variant	Exon 2 of 2		ENSP00000493417.1	Q8NGG0
OR8J3	ENST00000641489.1 link	n.289T>A		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000574

AC:

AN:

1394606

Hom.:

Cov.:

AF XY:

0.00000865

AC XY:

AN XY:

693602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31342

American (AMR)

AF:

0.00

AC:

AN:

37534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23288

East Asian (EAS)

AF:

0.00

AC:

AN:

39274

South Asian (SAS)

AF:

0.00

AC:

AN:

78396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52112

Middle Eastern (MID)

AF:

0.00127

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069352

Other (OTH)

AF:

0.00

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 12, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.940T>A (p.S314T) alteration is located in exon 1 (coding exon 1) of the OR8J3 gene. This alteration results from a T to A substitution at nucleotide position 940, causing the serine (S) at amino acid position 314 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.018

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.0027

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.17

.;.;T

M_CAP

Benign

0.00099

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

-2.2

PrimateAI

Benign

0.33

PROVEAN

Benign

0.26

.;.;N

REVEL

Benign

0.0090

Sift

Benign

0.97

.;.;T

Sift4G

Benign

0.78

.;.;T

Polyphen

0.0

B;B;B

Vest4

0.065

MutPred

0.20

Loss of ubiquitination at K313 (P = 0.0738);Loss of ubiquitination at K313 (P = 0.0738);Loss of ubiquitination at K313 (P = 0.0738);

MVP

0.10

MPC

0.0094

ClinPred

0.051

GERP RS

-1.0

Varity_R

0.026

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-56136779-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over