1-158399250-A-G

Variant summary

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

The NM_001004475.1(OR10T2):ā€‹c.217T>Cā€‹(p.Cys73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., cov: 32)
Exomes š‘“: 0.00026 ( 0 hom. )

Consequence

OR10T2
NM_001004475.1 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0370
Variant links:
Genes affected
OR10T2 (HGNC:14816): (olfactory receptor family 10 subfamily T 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. [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=0.24433488).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR10T2NM_001004475.1 linkuse as main transcriptc.217T>C p.Cys73Arg missense_variant 1/1 ENST00000334438.1 NP_001004475.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR10T2ENST00000334438.1 linkuse as main transcriptc.217T>C p.Cys73Arg missense_variant 1/1 NM_001004475.1 ENSP00000334115 P1

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.000426
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000164
AC:
41
AN:
250742
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135496
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000247
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000257
AC:
375
AN:
1461786
Hom.:
0
Cov.:
35
AF XY:
0.000260
AC XY:
189
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000268
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:
0.000317
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000455
Hom.:
0
Bravo
AF:
0.000212
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000222
AC:
27
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

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 GeneticsDec 07, 2021The c.217T>C (p.C73R) alteration is located in exon 1 (coding exon 1) of the OR10T2 gene. This alteration results from a T to C substitution at nucleotide position 217, causing the cysteine (C) at amino acid position 73 to be replaced by an arginine (R). 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
Pathogenic
0.75
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.028
T
Eigen
Benign
0.0091
Eigen_PC
Benign
-0.055
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.6
H
MutationTaster
Benign
0.97
N
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.36
B
Vest4
0.50
MVP
0.73
MPC
0.0092
ClinPred
0.27
T
GERP RS
3.6
Varity_R
0.95
gMVP
0.27

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

LitVar

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

Other links and lift over

dbSNP: rs200488972; hg19: chr1-158369040; COSMIC: COSV57781032; API