11-55651340-C-G

Variant names:

• chr11-55651340-C-G
• rs778705235
• NM_001004059.3:c.437C>G

Variant summary

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

The NM_001004059.3(OR4S2):​c.437C>G​(p.Thr146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T146M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 25)
• Consequence: OR4S2 NM_001004059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 0 publications found

Genes affected

OR4S2 (HGNC:15183): (olfactory receptor family 4 subfamily S member 2) 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 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
OR4S2	NM_001004059.3	c.437C>G	p.Thr146Arg	missense_variant	Exon 2 of 2	ENST00000641692.1	NP_001004059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4S2	ENST00000641692.1	c.437C>G	p.Thr146Arg	missense_variant	Exon 2 of 2		NM_001004059.3	ENSP00000493389.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.0061
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;M
PhyloP100		0.16
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		0.99	D;D
Vest4		0.26
MutPred		0.83		Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);
MVP		0.60
MPC		0.25
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.61
gMVP		0.69
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

dbSNP: rs778705235; hg19: chr11-55418816;