3-98469841-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004736.4(OR5K1):ā€‹c.265A>Gā€‹(p.Asn89Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,613,318 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N89S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0031 ( 1 hom., cov: 32)
Exomes š‘“: 0.00024 ( 3 hom. )

Consequence

OR5K1
NM_001004736.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.58
Variant links:
Genes affected
OR5K1 (HGNC:8349): (olfactory receptor family 5 subfamily K 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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0094227195).
BP6
Variant 3-98469841-A-G is Benign according to our data. Variant chr3-98469841-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2356179.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR5K1NM_001004736.4 linkuse as main transcriptc.265A>G p.Asn89Asp missense_variant 2/2 ENST00000642057.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR5K1ENST00000642057.1 linkuse as main transcriptc.265A>G p.Asn89Asp missense_variant 2/2 NM_001004736.4 P1
OR5K1ENST00000332650.5 linkuse as main transcriptc.265A>G p.Asn89Asp missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.00304
AC:
462
AN:
152030
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000918
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.000199
AC:
50
AN:
251238
Hom.:
0
AF XY:
0.000191
AC XY:
26
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.00198
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000237
AC:
346
AN:
1461168
Hom.:
3
Cov.:
31
AF XY:
0.000208
AC XY:
151
AN XY:
726946
show subpopulations
Gnomad4 AFR exome
AF:
0.00418
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00320
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.000447
GnomAD4 genome
AF:
0.00308
AC:
468
AN:
152150
Hom.:
1
Cov.:
32
AF XY:
0.00268
AC XY:
199
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0105
Gnomad4 AMR
AF:
0.000917
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00197
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 11, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.77
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.021
DANN
Benign
0.21
DEOGEN2
Benign
0.0029
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.030
.;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.0094
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.41
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.44
.;N
REVEL
Benign
0.033
Sift
Benign
1.0
.;T
Sift4G
Benign
1.0
.;T
Polyphen
0.0
B;B
Vest4
0.073
MVP
0.24
MPC
0.016
ClinPred
0.00072
T
GERP RS
-0.15
Varity_R
0.045
gMVP
0.021

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: rs901994567; hg19: chr3-98188685; API