1-247712542-A-G

Variant names:

• chr1-247712542-A-G
• NM_001005286.2:c.214T>C

Variant summary

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

The NM_001005286.2(OR6F1):​c.214T>C​(p.Trp72Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR6F1 NM_001005286.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.259
• Publications: 0 publications found

Genes affected

OR6F1 (HGNC:15027): (olfactory receptor family 6 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. [provided by RefSeq, Jul 2008]

ENSG00000239395 (HGNC:):

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=0.261906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6F1	NM_001005286.2	c.214T>C	p.Trp72Arg	missense_variant	Exon 3 of 3	ENST00000641470.1	NP_001005286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6F1	ENST00000641470.1	c.214T>C	p.Trp72Arg	missense_variant	Exon 3 of 3		NM_001005286.2	ENSP00000493342.1
ENSG00000239395	ENST00000419891.1	c.*38-455T>C		intron_variant	Intron 2 of 2	3		ENSP00000493458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.214T>C (p.W72R) alteration is located in exon 1 (coding exon 1) of the OR6F1 gene. This alteration results from a T to C substitution at nucleotide position 214, causing the tryptophan (W) at amino acid position 72 to be replaced by an arginine (R). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.73	.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	M;M;M
PhyloP100		0.26
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.3	.;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	.;.;D
Sift4G	Uncertain	0.017	.;.;D
Polyphen		0.48	P;P;P
Vest4		0.21
MutPred		0.59		Gain of methylation at W72 (P = 0.0359);Gain of methylation at W72 (P = 0.0359);Gain of methylation at W72 (P = 0.0359);
MVP		0.70
MPC		0.66
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.92
gMVP		0.51
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-247875844;