1-247814969-A-G

Variant summary

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

The NM_001001966.2(OR14A16):ā€‹c.761T>Cā€‹(p.Ile254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

OR14A16
NM_001001966.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.492
Variant links:
Genes affected
OR14A16 (HGNC:15022): (olfactory receptor family 14 subfamily A member 16) 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=0.018353283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR14A16NM_001001966.2 linkuse as main transcriptc.761T>C p.Ile254Thr missense_variant 3/3 ENST00000641093.1 NP_001001966.1 Q8NHC5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR14A16ENST00000641093.1 linkuse as main transcriptc.761T>C p.Ile254Thr missense_variant 3/3 NM_001001966.2 ENSP00000493024.1 Q8NHC5

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000223
AC:
56
AN:
251130
Hom.:
0
AF XY:
0.000265
AC XY:
36
AN XY:
135748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00328
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000176
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000140
AC:
204
AN:
1461762
Hom.:
0
Cov.:
34
AF XY:
0.000160
AC XY:
116
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00394
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000755
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000444
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 GeneticsJun 07, 2022The c.761T>C (p.I254T) alteration is located in exon 1 (coding exon 1) of the OR14A16 gene. This alteration results from a T to C substitution at nucleotide position 761, causing the isoleucine (I) at amino acid position 254 to be replaced by a threonine (T). 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
0.069
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
10
DANN
Benign
0.86
DEOGEN2
Benign
0.010
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.80
.;T
M_CAP
Benign
0.00065
T
MetaRNN
Benign
0.018
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-2.5
.;D
REVEL
Benign
0.039
Sift
Uncertain
0.016
.;D
Sift4G
Uncertain
0.023
.;D
Polyphen
0.030
B;B
Vest4
0.085
MVP
0.014
MPC
0.12
ClinPred
0.034
T
GERP RS
-0.26
Varity_R
0.15
gMVP
0.048

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: rs201060319; hg19: chr1-247978271; COSMIC: COSV99052276; API