Variant 12-55400791-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005518.1(OR6C65):c.263C>A(p.Thr88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,612,954 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

OR6C65
NM_001005518.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

OR6C65 (HGNC:31295): (olfactory receptor family 6 subfamily C member 65) 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]

OR6C65 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00903663).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C65	NM_001005518.1 linkuse as main transcript	c.263C>A	p.Thr88Lys	missense_variant	1/1	ENST00000379665.3	NP_001005518.1	A6NJZ3A0A126GW71

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C65	ENST00000379665.3 linkuse as main transcript	c.263C>A	p.Thr88Lys	missense_variant	1/1	6	NM_001005518.1	ENSP00000368986.2		A6NJZ3

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00117

AC:

294

AN:

250480

Hom.:

AF XY:

0.00134

AC XY:

181

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00103

AC:

1498

AN:

1460654

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

795

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000998

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152300

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00131

AC:

159

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 07, 2024

The c.263C>A (p.T88K) alteration is located in exon 1 (coding exon 1) of the OR6C65 gene. This alteration results from a C to A substitution at nucleotide position 263, causing the threonine (T) at amino acid position 88 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

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0010

DANN

Benign

0.75

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.33

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

PrimateAI

Benign

0.19

PROVEAN

Benign

3.9

REVEL

Benign

0.085

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.048

MVP

0.014

MPC

0.023

ClinPred

0.011

GERP RS

-4.9

Varity_R

0.026

gMVP

0.085

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