2-240045243-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173351.2(OR6B3):ā€‹c.830T>Gā€‹(p.Leu277Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00015 ( 0 hom., cov: 33)
Exomes š‘“: 0.00014 ( 1 hom. )

Consequence

OR6B3
NM_173351.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16
Variant links:
Genes affected
OR6B3 (HGNC:15042): (olfactory receptor family 6 subfamily B 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR6B3NM_173351.2 linkuse as main transcriptc.830T>G p.Leu277Trp missense_variant 3/3 ENST00000641019.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR6B3ENST00000641019.2 linkuse as main transcriptc.830T>G p.Leu277Trp missense_variant 3/3 NM_173351.2 P1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000284
AC:
71
AN:
249586
Hom.:
0
AF XY:
0.000288
AC XY:
39
AN XY:
135410
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00586
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000971
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000143
AC:
209
AN:
1461882
Hom.:
1
Cov.:
32
AF XY:
0.000122
AC XY:
89
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00562
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000277
Hom.:
1
Bravo
AF:
0.000144
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000607
AC:
5
ExAC
AF:
0.000232
AC:
28
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

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 GeneticsJun 27, 2022The c.830T>G (p.L277W) alteration is located in exon 1 (coding exon 1) of the OR6B3 gene. This alteration results from a T to G substitution at nucleotide position 830, causing the leucine (L) at amino acid position 277 to be replaced by a tryptophan (W). 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
0.29
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
23
DANN
Benign
0.96
DEOGEN2
Benign
0.020
T;T
Eigen
Uncertain
0.38
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.93
D;.
M_CAP
Benign
0.00063
T
MetaRNN
Benign
0.016
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Pathogenic
3.3
M;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-4.0
D;.
REVEL
Benign
0.14
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0050
D;.
Polyphen
0.99
D;D
Vest4
0.38
MVP
0.74
MPC
2.1
ClinPred
0.25
T
GERP RS
4.1
Varity_R
0.74
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.41
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.41
Position offset: 0

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: rs199592854; hg19: chr2-240984660; COSMIC: COSV105186562; API