11-5200357-C-G

Variant summary

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

The NM_001004760.3(OR51V1):​c.326G>C​(p.Gly109Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OR51V1
NM_001004760.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.994
Variant links:
Genes affected
OR51V1 (HGNC:19597): (olfactory receptor family 51 subfamily V 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]

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=0.063093156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR51V1NM_001004760.3 linkc.326G>C p.Gly109Ala missense_variant Exon 1 of 1 ENST00000641270.1 NP_001004760.3 Q9H2C8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR51V1ENST00000641270.1 linkc.326G>C p.Gly109Ala missense_variant Exon 1 of 1 NM_001004760.3 ENSP00000492968.1 A0A286YET0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461650
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
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
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.344G>C (p.G115A) alteration is located in exon 1 (coding exon 1) of the OR51V1 gene. This alteration results from a G to C substitution at nucleotide position 344, causing the glycine (G) at amino acid position 115 to be replaced by an alanine (A). 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
0.14
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0031
.;T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.0050
.;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.61
.;N
REVEL
Benign
0.073
Sift
Benign
0.53
.;T
Sift4G
Benign
0.39
.;T
Polyphen
0.33
.;B
Vest4
0.11
MutPred
0.26
.;Gain of glycosylation at S110 (P = 0.2987);
MVP
0.17
ClinPred
0.26
T
GERP RS
3.6
Varity_R
0.096
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr11-5221587; API