chr11-58031316-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001005186.2(OR6Q1):ā€‹c.364A>Gā€‹(p.Met122Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

OR6Q1
NM_001005186.2 missense

Scores

7
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.77
Variant links:
Genes affected
OR6Q1 (HGNC:15302): (olfactory receptor family 6 subfamily Q 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]
OR9Q1 (HGNC:14724): (olfactory receptor family 9 subfamily Q 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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR6Q1NM_001005186.2 linkuse as main transcriptc.364A>G p.Met122Val missense_variant 1/1 ENST00000302622.4 NP_001005186.2
OR9Q1NM_001005212.4 linkuse as main transcriptc.-93+7212A>G intron_variant ENST00000335397.3 NP_001005212.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR6Q1ENST00000302622.4 linkuse as main transcriptc.364A>G p.Met122Val missense_variant 1/1 NM_001005186.2 ENSP00000307734 P1
OR9Q1ENST00000335397.3 linkuse as main transcriptc.-93+7212A>G intron_variant NM_001005212.4 ENSP00000334934 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461866
Hom.:
0
Cov.:
37
AF XY:
0.00000138
AC XY:
1
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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.:
32

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 submitterclinical testingAmbry GeneticsAug 12, 2022The c.364A>G (p.M122V) alteration is located in exon 1 (coding exon 1) of the OR6Q1 gene. This alteration results from a A to G substitution at nucleotide position 364, causing the methionine (M) at amino acid position 122 to be replaced by a valine (V). 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
0.27
BayesDel_addAF
Benign
-0.023
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
T
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.9
H
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.60
Loss of stability (P = 0.2337);
MVP
0.54
MPC
0.20
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.70
gMVP
0.24

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.

Other links and lift over

dbSNP: rs1590543421; hg19: chr11-57798788; API