rs746095013

Variant summary

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

The NM_001005179.4(OR56A4):​c.281C>T​(p.Ser94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,104 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S94W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

OR56A4
NM_001005179.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.738
Variant links:
Genes affected
OR56A4 (HGNC:14791): (olfactory receptor family 56 subfamily A member 4) 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]
OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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=0.1029093).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR56A4NM_001005179.4 linkc.281C>T p.Ser94Leu missense_variant Exon 3 of 3 ENST00000641156.1 NP_001005179.3 Q8NGH8A0A126GWQ5A0A2C9F2M6
OR56A3XM_047426926.1 linkc.*469-1008G>A intron_variant Intron 3 of 5 XP_047282882.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR56A4ENST00000641156.1 linkc.281C>T p.Ser94Leu missense_variant Exon 3 of 3 NM_001005179.4 ENSP00000492932.1 Q8NGH8
OR56A4ENST00000330728.4 linkc.437C>T p.Ser146Leu missense_variant Exon 1 of 1 6 ENSP00000328215.4 A0A2C9F2M6
OR56A4ENST00000641279.1 linkc.281C>T p.Ser94Leu missense_variant Exon 1 of 1 ENSP00000492934.1 Q8NGH8
OR56A4ENST00000641835.1 linkc.281C>T p.Ser94Leu missense_variant Exon 2 of 2 ENSP00000493371.1 Q8NGH8

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251422
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
12
DANN
Benign
0.91
DEOGEN2
Benign
0.12
T;T;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.24
.;.;T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.2
L;L;L;.
PrimateAI
Benign
0.19
T
PROVEAN
Uncertain
-2.6
.;.;.;D
REVEL
Benign
0.038
Sift
Benign
0.067
.;.;.;T
Sift4G
Benign
0.14
.;.;.;T
Polyphen
0.0080
B;B;B;.
Vest4
0.083
MutPred
0.40
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP
0.20
MPC
0.068
ClinPred
0.034
T
GERP RS
2.3
Varity_R
0.052
gMVP
0.082

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: rs746095013; hg19: chr11-6023942; COSMIC: COSV58109498; API