chr2-240045368-C-G

Variant names:

• chr2-240045368-C-G
• NM_173351.2:c.705G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173351.2(OR6B3):​c.705G>C​(p.Trp235Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR6B3 NM_173351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.304
• Publications: 0 publications found

Genes affected

OR6B3 (HGNC:15042): (olfactory receptor family 6 subfamily B member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10962096).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B3	NM_173351.2	MANE Select	c.705G>C	p.Trp235Cys	missense	Exon 3 of 3	NP_775486.1	Q8NGW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B3	ENST00000641019.2	MANE Select	c.705G>C	p.Trp235Cys	missense	Exon 3 of 3	ENSP00000493035.1	Q8NGW1
	OR6B3	ENST00000943407.1		c.705G>C	p.Trp235Cys	missense	Exon 2 of 2	ENSP00000613466.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.11	T
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Benign	0.020	N
PhyloP100		-0.30
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.099
Sift	Benign	0.18	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.21
MutPred		0.40		Gain of methylation at R236 (P = 0.0334)
MVP		0.35
MPC		2.1
ClinPred		0.64	D
GERP RS		3.2
Varity_R		0.33
gMVP		0.35
Mutation Taster		=87/13	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: chr2-240984785; COSMIC: COSV107401731;