Variant 11-6795387-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003696.3(OR6A2):c.322T>C(p.Phe108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OR6A2
NM_003696.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

OR6A2 (HGNC:15301): (olfactory receptor family 6 subfamily A member 2) 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]

OR6A2 links:

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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=0.36099267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR6A2	NM_003696.3 linkuse as main transcript	c.322T>C	p.Phe108Leu	missense_variant	2/2	ENST00000641196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR6A2	ENST00000641196.1 linkuse as main transcript	c.322T>C	p.Phe108Leu	missense_variant	2/2		NM_003696.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727194

show subpopulations

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:

0.00000180

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

May 26, 2024

The c.322T>C (p.F108L) alteration is located in exon 1 (coding exon 1) of the OR6A2 gene. This alteration results from a T to C substitution at nucleotide position 322, causing the phenylalanine (F) at amino acid position 108 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

0.70

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.038

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.95

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.0

.;D

REVEL

Benign

0.11

Sift

Benign

0.094

.;T

Sift4G

Benign

0.088

.;T

Polyphen

1.0

D;D

Vest4

0.15

MutPred

0.34

Loss of catalytic residue at F108 (P = 0.0549);Loss of catalytic residue at F108 (P = 0.0549);

MVP

0.27

MPC

0.024

ClinPred

1.0

GERP RS

5.1

Varity_R

0.61

gMVP

0.21

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

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