Variant chr12-55320619-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005182.2(OR6C1):c.20T>C(p.Ile7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR6C1
NM_001005182.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

OR6C1 (HGNC:8355): (olfactory receptor family 6 subfamily C 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]

OR6C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2786009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C1	NM_001005182.2 linkuse as main transcript	c.20T>C	p.Ile7Thr	missense_variant	2/2	ENST00000642104.1	NP_001005182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C1	ENST00000642104.1 linkuse as main transcript	c.20T>C	p.Ile7Thr	missense_variant	2/2		NM_001005182.2	ENSP00000492978	P1
OR6C1	ENST00000379668.3 linkuse as main transcript	c.20T>C	p.Ile7Thr	missense_variant	1/1			ENSP00000368990	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721028

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:

0.00

GnomAD4 genome

Cov.:

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

Dec 14, 2022

The c.20T>C (p.I7T) alteration is located in exon 1 (coding exon 1) of the OR6C1 gene. This alteration results from a T to C substitution at nucleotide position 20, causing the isoleucine (I) at amino acid position 7 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.7

DANN

Benign

0.91

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.33

.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.95

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

.;N

REVEL

Benign

0.074

Sift

Benign

0.057

.;T

Sift4G

Uncertain

0.035

.;D

Polyphen

0.0010

B;B

Vest4

0.034

MutPred

0.78

Gain of disorder (P = 0.0146);Gain of disorder (P = 0.0146);

MVP

0.20

MPC

0.013

ClinPred

0.043

GERP RS

2.9

Varity_R

0.045

gMVP

0.028

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over