11-58439542-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004733.3(OR5B12):ā€‹c.610A>Gā€‹(p.Asn204Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000099 ( 0 hom., cov: 32)
Exomes š‘“: 0.000073 ( 0 hom. )

Consequence

OR5B12
NM_001004733.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.278
Variant links:
Genes affected
OR5B12 (HGNC:15432): (olfactory receptor family 5 subfamily B member 12) 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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09180918).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5B12NM_001004733.3 linkuse as main transcriptc.610A>G p.Asn204Asp missense_variant 2/2 ENST00000641921.2 NP_001004733.1 Q96R08

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5B12ENST00000641921.2 linkuse as main transcriptc.610A>G p.Asn204Asp missense_variant 2/2 NM_001004733.3 ENSP00000493263.1 Q96R08
OR5B12ENST00000302572.2 linkuse as main transcriptc.610A>G p.Asn204Asp missense_variant 1/16 ENSP00000306657.2 Q96R08

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000719
AC:
18
AN:
250280
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135286
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000725
AC:
106
AN:
1461186
Hom.:
0
Cov.:
32
AF XY:
0.0000839
AC XY:
61
AN XY:
726918
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.0000854
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000138
Hom.:
0
Bravo
AF:
0.0000907
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000296

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 GeneticsAug 12, 2022The c.610A>G (p.N204D) alteration is located in exon 1 (coding exon 1) of the OR5B12 gene. This alteration results from a A to G substitution at nucleotide position 610, causing the asparagine (N) at amino acid position 204 to be replaced by an aspartic acid (D). 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
-0.44
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T;T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.033
.;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.092
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-4.0
.;D
REVEL
Benign
0.065
Sift
Benign
0.097
.;T
Sift4G
Benign
0.14
.;T
Polyphen
0.35
B;B
Vest4
0.36
MVP
0.21
MPC
0.042
ClinPred
0.089
T
GERP RS
3.1
Varity_R
0.32
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144827284; hg19: chr11-58207015; API