17-3215636-C-A

Variant summary

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

The NM_014565.3(OR1A1):​c.16C>A​(p.Gln6Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,618 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

OR1A1
NM_014565.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.659
Variant links:
Genes affected
OR1A1 (HGNC:8179): (olfactory receptor family 1 subfamily A 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 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=0.037311703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1A1NM_014565.3 linkc.16C>A p.Gln6Lys missense_variant 4/4 ENST00000641732.2 NP_055380.2 Q9P1Q5A0A126GWA2
OR1A1NM_001386104.1 linkc.16C>A p.Gln6Lys missense_variant 2/2 NP_001373033.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1A1ENST00000641732.2 linkc.16C>A p.Gln6Lys missense_variant 4/4 NM_014565.3 ENSP00000493179.1 Q9P1Q5
OR1A1ENST00000641322.1 linkc.16C>A p.Gln6Lys missense_variant 2/2 ENSP00000492897.1 Q9P1Q5

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250704
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135480
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460470
Hom.:
0
Cov.:
30
AF XY:
0.00000551
AC XY:
4
AN XY:
726406
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

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 GeneticsApr 18, 2024The c.16C>A (p.Q6K) alteration is located in exon 1 (coding exon 1) of the OR1A1 gene. This alteration results from a C to A substitution at nucleotide position 16, causing the glutamine (Q) at amino acid position 6 to be replaced by a lysine (K). 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
0.075
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
9.2
DANN
Benign
0.92
DEOGEN2
Benign
0.0087
T;T;T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.092
N
LIST_S2
Benign
0.56
.;.;T
M_CAP
Benign
0.00075
T
MetaRNN
Benign
0.037
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.3
M;M;M
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.9
.;.;N
REVEL
Benign
0.026
Sift
Benign
0.077
.;.;T
Sift4G
Benign
0.077
.;.;T
Polyphen
0.010
B;B;B
Vest4
0.084
MutPred
0.36
Gain of ubiquitination at Q6 (P = 0.0077);Gain of ubiquitination at Q6 (P = 0.0077);Gain of ubiquitination at Q6 (P = 0.0077);
MVP
0.42
MPC
0.028
ClinPred
0.061
T
GERP RS
1.1
Varity_R
0.066
gMVP
0.21

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: rs776562506; hg19: chr17-3118930; API