2-240045432-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173351.2(OR6B3):​c.641C>A​(p.Thr214Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,228 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 (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000070 ( 1 hom. )

Consequence

OR6B3
NM_173351.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0315229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR6B3NM_173351.2 linkuse as main transcriptc.641C>A p.Thr214Asn missense_variant 3/3 ENST00000641019.2 NP_775486.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR6B3ENST00000641019.2 linkuse as main transcriptc.641C>A p.Thr214Asn missense_variant 3/3 NM_173351.2 ENSP00000493035 P1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152230
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000152
AC:
38
AN:
249560
Hom.:
0
AF XY:
0.000192
AC XY:
26
AN XY:
135410
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00124
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000705
AC:
103
AN:
1461880
Hom.:
1
Cov.:
36
AF XY:
0.0000935
AC XY:
68
AN XY:
727244
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:
0.00115
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152348
Hom.:
0
Cov.:
29
AF XY:
0.000121
AC XY:
9
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.000206
AC:
25
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 GeneticsMay 23, 2023The c.641C>A (p.T214N) alteration is located in exon 1 (coding exon 1) of the OR6B3 gene. This alteration results from a C to A substitution at nucleotide position 641, causing the threonine (T) at amino acid position 214 to be replaced by an asparagine (N). 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
0.28
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.55
T;.
M_CAP
Benign
0.00098
T
MetaRNN
Benign
0.032
T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.5
M;M
MutationTaster
Benign
0.71
D
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-4.0
D;.
REVEL
Benign
0.095
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.032
D;.
Polyphen
1.0
D;D
Vest4
0.24
MutPred
0.52
Loss of glycosylation at T214 (P = 0.0569);Loss of glycosylation at T214 (P = 0.0569);
MVP
0.53
MPC
1.8
ClinPred
0.29
T
GERP RS
4.1
Varity_R
0.40
gMVP
0.61

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: rs535362001; hg19: chr2-240984849; API