6-29112047-T-C

Variant names:

• chr6-29112047-T-C
• rs1762148012
• NM_001005216.4:c.157T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005216.4(OR2J3):​c.157T>C​(p.Tyr53His) 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. 14/19 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: OR2J3 NM_001005216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.57

Genes affected

OR2J3 (HGNC:8261): (olfactory receptor family 2 subfamily J member 3) This gene encodes a G-protein-coupled receptor (GPCR) that functions as an olfactory receptor. Olfactory receptors interact with odorant molecules in the nose to initiate a neuronal response that triggers the perception of a smell. The protein encoded by this gene responds to cis-3-hexen-1-ol, which is released by wounded plants, including cut grass. This gene is situated in a cluster of similar olfactory-receptor coding genes on chromosome 6. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040609002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2J3	NM_001005216.4	c.157T>C	p.Tyr53His	missense_variant	Exon 4 of 4	ENST00000641151.2	NP_001005216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2J3	ENST00000641151.2	c.157T>C	p.Tyr53His	missense_variant	Exon 4 of 4		NM_001005216.4	ENSP00000492961.1
OR2J3	ENST00000377169.2	c.157T>C	p.Tyr53His	missense_variant	Exon 1 of 1	6		ENSP00000366374.1
OR2J3	ENST00000641960.1	c.157T>C	p.Tyr53His	missense_variant	Exon 5 of 5			ENSP00000493439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157T>C (p.Y53H) alteration is located in exon 1 (coding exon 1) of the OR2J3 gene. This alteration results from a T to C substitution at nucleotide position 157, causing the tyrosine (Y) at amino acid position 53 to be replaced by a histidine (H). 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	0.073
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.0
DANN	Benign	0.58
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.30	.;.;T
M_CAP	Benign	0.00070	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.38	.;.;N
REVEL	Benign	0.11
Sift	Benign	0.56	.;.;T
Sift4G	Benign	0.54	.;.;T
Vest4		0.12
MutPred		0.24		Loss of stability (P = 0.0819);Loss of stability (P = 0.0819);Loss of stability (P = 0.0819);
MVP		0.055
MPC		0.14
ClinPred		0.050	T
GERP RS		2.8
gMVP		0.10

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

Publications

LitVar

Other links and lift over

dbSNP: rs1762148012; hg19: chr6-29079824;