Variant chr11-56346546-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002907.1(OR8K1):c.508T>C(p.Phe170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

OR8K1
NM_001002907.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540

Variant links:

Genes affected

OR8K1 (HGNC:14831): (olfactory receptor family 8 subfamily K 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]

OR8K1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018446952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8K1	NM_001002907.1 linkuse as main transcript	c.508T>C	p.Phe170Leu	missense_variant	1/1	ENST00000279783.5	NP_001002907.1	Q8NGG5A0A126GVZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8K1	ENST00000279783.5 linkuse as main transcript	c.508T>C	p.Phe170Leu	missense_variant	1/1	6	NM_001002907.1	ENSP00000279783.2		Q8NGG5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251122

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2022

The c.508T>C (p.F170L) alteration is located in exon 1 (coding exon 1) of the OR8K1 gene. This alteration results from a T to C substitution at nucleotide position 508, causing the phenylalanine (F) at amino acid position 170 to be replaced by a leucine (L). 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

0.61

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.076

M_CAP

Benign

0.0028

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.17

Sift

Uncertain

0.012

Sift4G

Benign

0.19

Polyphen

0.79

Vest4

0.17

MutPred

0.44

Loss of methylation at K171 (P = 0.0557);

MVP

0.12

MPC

0.099

ClinPred

0.25

GERP RS

5.0

Varity_R

0.61

gMVP

0.075

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over