17-3215879-T-G

Variant summary

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

The NM_014565.3(OR1A1):​c.259T>G​(p.Leu87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OR1A1
NM_014565.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -7.25
Variant links:
Genes affected
OR1A1 (HGNC:8179): (olfactory receptor family 1 subfamily A 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=0.0444265).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1A1NM_014565.3 linkc.259T>G p.Leu87Val missense_variant 4/4 ENST00000641732.2 NP_055380.2 Q9P1Q5A0A126GWA2
OR1A1NM_001386104.1 linkc.259T>G p.Leu87Val missense_variant 2/2 NP_001373033.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1A1ENST00000641732.2 linkc.259T>G p.Leu87Val missense_variant 4/4 NM_014565.3 ENSP00000493179.1 Q9P1Q5
OR1A1ENST00000641322.1 linkc.259T>G p.Leu87Val missense_variant 2/2 ENSP00000492897.1 Q9P1Q5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
32

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 GeneticsApr 06, 2023The c.259T>G (p.L87V) alteration is located in exon 1 (coding exon 1) of the OR1A1 gene. This alteration results from a T to G substitution at nucleotide position 259, causing the leucine (L) at amino acid position 87 to be replaced by a valine (V). 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
0.089
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.0080
DANN
Benign
0.74
DEOGEN2
Benign
0.0019
T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.21
.;.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.044
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.61
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.85
.;.;N
REVEL
Benign
0.16
Sift
Benign
0.77
.;.;T
Sift4G
Uncertain
0.037
.;.;D
Polyphen
0.0040
B;B;B
Vest4
0.056
MutPred
0.33
Gain of methylation at K90 (P = 0.0871);Gain of methylation at K90 (P = 0.0871);Gain of methylation at K90 (P = 0.0871);
MVP
0.56
MPC
0.025
ClinPred
0.054
T
GERP RS
-3.2
Varity_R
0.051
gMVP
0.030

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3119173; API