chr3-98168781-T-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001005515.2(OR5H15):āc.82T>Cā(p.Phe28Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,613,438 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00017 ( 2 hom., cov: 32)
Exomes š: 0.000060 ( 1 hom. )
Consequence
OR5H15
NM_001005515.2 missense
NM_001005515.2 missense
Scores
2
4
11
Clinical Significance
Conservation
PhyloP100: 6.89
Genes affected
OR5H15 (HGNC:31287): (olfactory receptor family 5 subfamily H member 15) 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 -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.120005876).
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OR5H15 | NM_001005515.2 | c.82T>C | p.Phe28Leu | missense_variant | 2/2 | ENST00000641450.1 | NP_001005515.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OR5H15 | ENST00000641450.1 | c.82T>C | p.Phe28Leu | missense_variant | 2/2 | NM_001005515.2 | ENSP00000493082 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152082Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250970Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135644
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461356Hom.: 1 Cov.: 35 AF XY: 0.0000385 AC XY: 28AN XY: 727006
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152082Hom.: 2 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74276
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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 29, 2024 | The c.82T>C (p.F28L) alteration is located in exon 1 (coding exon 1) of the OR5H15 gene. This alteration results from a T to C substitution at nucleotide position 82, causing the phenylalanine (F) at amino acid position 28 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D
Sift
Uncertain
.;D
Polyphen
P;.
MutPred
Gain of ubiquitination at K24 (P = 0.0853);Gain of ubiquitination at K24 (P = 0.0853);
ClinPred
D
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