2-240045432-G-T
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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
NM_173351.2 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 2.94
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]
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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 |
---|---|---|---|---|---|---|---|---|
OR6B3 | NM_173351.2 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
OR6B3 | ENST00000641019.2 | c.641C>A | p.Thr214Asn | missense_variant | 3/3 | NM_173351.2 | ENSP00000493035 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152230Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.000152 AC: 38AN: 249560Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135410
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GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461880Hom.: 1 Cov.: 36 AF XY: 0.0000935 AC XY: 68AN XY: 727244
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GnomAD4 genome AF: 0.0000656 AC: 10AN: 152348Hom.: 0 Cov.: 29 AF XY: 0.000121 AC XY: 9AN XY: 74500
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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 23, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
MutPred
Loss of glycosylation at T214 (P = 0.0569);Loss of glycosylation at T214 (P = 0.0569);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at