chr2-240045602-C-A

Variant summary

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

The NM_173351.2(OR6B3):​c.471G>T​(p.Met157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,487,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000027 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

OR6B3
NM_173351.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.133
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=0.043559372).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR6B3NM_173351.2 linkuse as main transcriptc.471G>T p.Met157Ile 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.471G>T p.Met157Ile missense_variant 3/3 NM_173351.2 ENSP00000493035 P1

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
150858
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000443
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000480
AC:
1
AN:
208200
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
113008
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000110
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000105
AC:
14
AN:
1336264
Hom.:
0
Cov.:
20
AF XY:
0.00000897
AC XY:
6
AN XY:
668684
show subpopulations
Gnomad4 AFR exome
AF:
0.0000323
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:
0.0000120
Gnomad4 OTH exome
AF:
0.0000178
GnomAD4 genome
AF:
0.0000265
AC:
4
AN:
150858
Hom.:
0
Cov.:
28
AF XY:
0.0000136
AC XY:
1
AN XY:
73590
show subpopulations
Gnomad4 AFR
AF:
0.0000245
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000443
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000835
AC:
1

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, 2021The c.471G>T (p.M157I) alteration is located in exon 1 (coding exon 1) of the OR6B3 gene. This alteration results from a G to T substitution at nucleotide position 471, causing the methionine (M) at amino acid position 157 to be replaced by an isoleucine (I). 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
0.21
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.7
DANN
Benign
0.93
DEOGEN2
Benign
0.0040
T;T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.10
T;.
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.63
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.55
N;.
REVEL
Benign
0.019
Sift
Benign
0.22
T;.
Sift4G
Benign
0.18
T;.
Polyphen
0.0020
B;B
Vest4
0.034
MutPred
0.30
Gain of catalytic residue at M157 (P = 0.0192);Gain of catalytic residue at M157 (P = 0.0192);
MVP
0.18
MPC
0.77
ClinPred
0.020
T
GERP RS
2.3
Varity_R
0.092
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs746623284; hg19: chr2-240985019; API