chr7-143960133-C-T

Variant names:

• chr7-143960133-C-T
• NM_012369.3:c.163C>T

Variant summary

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

The NM_012369.3(OR2F1):​c.163C>T​(p.Leu55Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2F1 NM_012369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

Genes affected

OR2F1 (HGNC:8246): (olfactory receptor family 2 subfamily F member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

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
OR2F1	NM_012369.3	c.163C>T	p.Leu55Phe	missense_variant	Exon 3 of 3	ENST00000641412.1	NP_036501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2F1	ENST00000641412.1	c.163C>T	p.Leu55Phe	missense_variant	Exon 3 of 3		NM_012369.3	ENSP00000493004.1
OR2F1	ENST00000624504.1	c.163C>T	p.Leu55Phe	missense_variant	Exon 1 of 1	6		ENSP00000485483.1
OR2F1	ENST00000470988.1	n.146+1025C>T		intron_variant	Intron 1 of 2	2
OR2F1	ENST00000641986.1	n.296+139C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>T (p.L55F) alteration is located in exon 1 (coding exon 1) of the OR2F1 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the leucine (L) at amino acid position 55 to be replaced by a phenylalanine (F). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0099	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Benign	0.28	T
Polyphen		1.0	D;D
MutPred		0.73		Loss of catalytic residue at L55 (P = 0.0101);Loss of catalytic residue at L55 (P = 0.0101);
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.87
gMVP		0.081

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr7-143657226;