1-158717391-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005327.3(OR6K3):c.725G>A(p.Gly242Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: OR6K3 NM_001005327.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0650

Genes affected

OR6K3 (HGNC:15030): (olfactory receptor family 6 subfamily K member 3) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13346246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR6K3	NM_001005327.3	c.725G>A	p.Gly242Asp	missense_variant	2/2	ENST00000368145.2
OR6K3	XM_047420296.1	c.725G>A	p.Gly242Asp	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR6K3	ENST00000368145.2	c.725G>A	p.Gly242Asp	missense_variant	2/2		NM_001005327.3	P1
OR6K3	ENST00000368146.1	c.773G>A	p.Gly258Asp	missense_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000559 AC: 14 AN: 250504 Hom.: 0 AF XY: 0.0000813 AC XY: 11 AN XY: 135348

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461502 Hom.: 0 Cov.: 36 AF XY: 0.0000330 AC XY: 24 AN XY: 727066

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: 0.000359

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000577 AC: 7

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

Jan 23, 2024

The c.725G>A (p.G242D) alteration is located in exon 1 (coding exon 1) of the OR6K3 gene. This alteration results from a G to A substitution at nucleotide position 725, causing the glycine (G) at amino acid position 242 to be replaced by an aspartic acid (D). 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	0.28
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	13
Dann	Uncertain	0.99
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.74	.;P
Vest4		0.18
MutPred		0.54		.;Loss of catalytic residue at C256 (P = 0.0629);
MVP		0.35
MPC		0.087
ClinPred		0.24	T
GERP RS		-7.5
Varity_R		0.45
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs764367736; hg19: chr1-158687181;