11-58118547-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001005211.2(OR9I1):c.898G>A(p.Ala300Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,612,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
OR9I1
NM_001005211.2 missense
NM_001005211.2 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: 1.21
Genes affected
OR9I1 (HGNC:14718): (olfactory receptor family 9 subfamily I 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]
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 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=0.060246676).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| OR9I1 | NM_001005211.2 | c.898G>A | p.Ala300Thr | missense_variant | 3/3 | ENST00000641439.1 | |
| OR9Q1 | NM_001005212.4 | c.-14-60884C>T | intron_variant | ENST00000335397.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OR9I1 | ENST00000641439.1 | c.898G>A | p.Ala300Thr | missense_variant | 3/3 | NM_001005211.2 | P1 | ||
| OR9Q1 | ENST00000335397.3 | c.-14-60884C>T | intron_variant | NM_001005212.4 | P1 | ||||
| OR9I1 | ENST00000641478.1 | c.898G>A | p.Ala300Thr | missense_variant | 3/3 | P1 |
Frequencies
GnomAD3 genomes 0.000125 AC: 19AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000336 AC: 84AN: 249682Hom.: 0 AF XY: 0.000400 AC XY: 54AN XY: 134878
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GnomAD4 exome AF: 0.000223 AC: 325AN: 1460666Hom.: 1 Cov.: 32 AF XY: 0.000226 AC XY: 164AN XY: 726606
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GnomAD4 genome 0.000118 AC: 18AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74456
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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 | Jul 09, 2021 | The c.898G>A (p.A300T) alteration is located in exon 1 (coding exon 1) of the OR9I1 gene. This alteration results from a G to A substitution at nucleotide position 898, causing the alanine (A) at amino acid position 300 to be replaced by a threonine (T). 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
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;N
PrimateAI
Benign
T
Polyphen
B;B;B
Vest4
0.27
MVP
0.15
MPC
0.017
ClinPred
T
GERP RS
Varity_R
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