6-29397207-A-C

Variant summary

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

The NM_013936.4(OR12D2):ā€‹c.508A>Cā€‹(p.Asn170His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 1 hom. )

Consequence

OR12D2
NM_013936.4 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.177
Variant links:
Genes affected
OR12D2 (HGNC:8178): (olfactory receptor family 12 subfamily D member 2) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]
OR5V1 (HGNC:13972): (olfactory receptor family 5 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 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=0.07217872).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR12D2NM_013936.4 linkuse as main transcriptc.508A>C p.Asn170His missense_variant 2/2 ENST00000642051.1 NP_039224.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR12D2ENST00000642051.1 linkuse as main transcriptc.508A>C p.Asn170His missense_variant 2/2 NM_013936.4 ENSP00000493463 P1
OR12D2ENST00000623183.1 linkuse as main transcriptc.508A>C p.Asn170His missense_variant 1/1 ENSP00000485112 P1
OR5V1ENST00000377154.1 linkuse as main transcriptc.-83+25400T>G intron_variant ENSP00000366359 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000812
AC:
2
AN:
246170
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134136
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1460778
Hom.:
1
Cov.:
44
AF XY:
0.0000124
AC XY:
9
AN XY:
726702
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000189
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

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 GeneticsMar 06, 2023The c.508A>C (p.N170H) alteration is located in exon 1 (coding exon 1) of the OR12D2 gene. This alteration results from a A to C substitution at nucleotide position 508, causing the asparagine (N) at amino acid position 170 to be replaced by a histidine (H). 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
0.086
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
9.0
DANN
Benign
0.97
DEOGEN2
Benign
0.0082
T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.51
.;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.9
L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.22
T
Polyphen
0.054
B;B
MutPred
0.54
Loss of solvent accessibility (P = 0.1744);Loss of solvent accessibility (P = 0.1744);
ClinPred
0.070
T
GERP RS
-0.049
Varity_R
0.094
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs767949185; hg19: chr6-29364984; API