Variant chr12-55332190-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001388498.1(OR6C3):c.490G>C(p.Asp164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,932 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

OR6C3
NM_001388498.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.185

Variant links:

Genes affected

OR6C3 (HGNC:15437): (olfactory receptor family 6 subfamily C 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]

OR6C3 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=0.04152623).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C3	NM_001388498.1 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	2/2	ENST00000641740.2	NP_001375427.1
OR6C3	NM_054104.2 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	2/2		NP_473445.1	Q9NZP0A0A126GW44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C3	ENST00000641740.2 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	2/2		NM_001388498.1	ENSP00000493380.1		Q9NZP0
OR6C3	ENST00000641364.1 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	2/2			ENSP00000493034.1		Q9NZP0

Frequencies

GnomAD3 genomes

AF:

0.000566

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000545

AC:

137

AN:

251272

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00109

AC:

1589

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

756

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.000565

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.000608

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.00154

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 02, 2024

The c.490G>C (p.D164H) alteration is located in exon 1 (coding exon 1) of the OR6C3 gene. This alteration results from a G to C substitution at nucleotide position 490, causing the aspartic acid (D) at amino acid position 164 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.34

.;.;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.91

L;L;L

PrimateAI

Benign

0.20

PROVEAN

Pathogenic

-5.7

.;.;D

REVEL

Benign

0.097

Sift

Uncertain

0.0050

.;.;D

Sift4G

Uncertain

0.060

.;.;T

Polyphen

0.053

B;B;B

Vest4

0.18

MVP

0.62

MPC

0.014

ClinPred

0.12

GERP RS

4.4

Varity_R

0.43

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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