chr1-158547566-A-T

Position:

• chr1-158547566-A-T

Variant summary

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

The NM_001005189.2(OR6Y1):​c.540T>A​(p.Asn180Lys) 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 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N180S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR6Y1 NM_001005189.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48

Genes affected

OR6Y1 (HGNC:14823): (olfactory receptor family 6 subfamily Y 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]

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
OR6Y1	NM_001005189.2	c.540T>A	p.Asn180Lys	missense_variant	2/2	ENST00000641622.1	NP_001005189.1
OR6Y1	NM_001386050.1	c.540T>A	p.Asn180Lys	missense_variant	2/2		NP_001372979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6Y1	ENST00000641622.1	c.540T>A	p.Asn180Lys	missense_variant	2/2		NM_001005189.2	ENSP00000492894.1
OR6Y1	ENST00000641282.1	c.540T>A	p.Asn180Lys	missense_variant	2/2			ENSP00000493253.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461522 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Sep 27, 2022

The c.540T>A (p.N180K) alteration is located in exon 1 (coding exon 1) of the OR6Y1 gene. This alteration results from a T to A substitution at nucleotide position 540, causing the asparagine (N) at amino acid position 180 to be replaced by a lysine (K). 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	0.56
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T;T;T
Eigen	Benign	-0.0077
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.93	.;.;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Uncertain	-0.087	T
MutationAssessor	Uncertain	2.9	M;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.9	.;.;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	.;.;D
Sift4G	Uncertain	0.018	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.67
MutPred		0.66		Gain of methylation at N180 (P = 0.0016);Gain of methylation at N180 (P = 0.0016);Gain of methylation at N180 (P = 0.0016);
MVP		0.88
MPC		0.16
ClinPred		1.0	D
GERP RS		-2.3
Varity_R		0.86
gMVP		0.11

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: chr1-158517356;