1-158755086-A-T

Position:

• chr1-158755086-A-T

Variant summary

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

The NM_001005184.2(OR6K6):​c.199A>T​(p.Ile67Phe) 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: 32)
• Consequence: OR6K6 NM_001005184.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.255

Genes affected

OR6K6 (HGNC:15033): (olfactory receptor family 6 subfamily K member 6) 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]

OR6N1 (HGNC:):

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/exons	MANE	Protein	UniProt
OR6K6	NM_001005184.2	c.199A>T	p.Ile67Phe	missense_variant	1/1	ENST00000641861.1	NP_001005184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6K6	ENST00000641861.1	c.199A>T	p.Ile67Phe	missense_variant	1/1		NM_001005184.2	ENSP00000493180.1
OR6N1	ENST00000641189.1	n.176-7187T>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.271A>T (p.I91F) alteration is located in exon 1 (coding exon 1) of the OR6K6 gene. This alteration results from a A to T substitution at nucleotide position 271, causing the isoleucine (I) at amino acid position 91 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	Benign	0.26
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	.;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Benign	0.27
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0050	.;D
Polyphen		1.0	.;D
Vest4		0.31
MutPred		0.54		.;Loss of catalytic residue at I91 (P = 0.2355);
MVP		0.70
MPC		0.11
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.42
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1656955836; hg19: chr1-158724876;