11-56376251-T-G

Variant summary

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

The NM_001005204.1(OR8U1):ā€‹c.628T>Gā€‹(p.Ser210Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000098 ( 0 hom., cov: 55)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

OR8U1
NM_001005204.1 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.201
Variant links:
Genes affected
OR8U1 (HGNC:19611): (olfactory receptor family 8 subfamily U 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 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=0.19271544).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR8U1NM_001005204.1 linkc.628T>G p.Ser210Ala missense_variant 1/1 ENST00000302270.1 NP_001005204.1 Q8NH10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR8U1ENST00000302270.1 linkc.628T>G p.Ser210Ala missense_variant 1/16 NM_001005204.1 ENSP00000304188.1 Q8NH10

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152302
Hom.:
0
Cov.:
55
show subpopulations
Gnomad AFR
AF:
0.000313
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000201
AC:
5
AN:
249304
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135274
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.0000580
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461872
Hom.:
0
Cov.:
131
AF XY:
0.00000963
AC XY:
7
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.000134
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000984
AC:
15
AN:
152420
Hom.:
0
Cov.:
55
AF XY:
0.0000939
AC XY:
7
AN XY:
74538
show subpopulations
Gnomad4 AFR
AF:
0.000312
Gnomad4 AMR
AF:
0.000131
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:
0.0000853
Hom.:
0
ExAC
AF:
0.0000248
AC:
3

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 GeneticsJul 09, 2021The c.628T>G (p.S210A) alteration is located in exon 1 (coding exon 1) of the OR8U1 gene. This alteration results from a T to G substitution at nucleotide position 628, causing the serine (S) at amino acid position 210 to be replaced by an alanine (A). 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
0.13
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0078
T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.99
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.23
Sift
Benign
0.039
D
Sift4G
Benign
0.13
T
Polyphen
0.93
P
Vest4
0.38
MVP
0.57
MPC
0.43
ClinPred
0.31
T
GERP RS
4.4
Varity_R
0.21
gMVP
0.092

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs553109678; hg19: chr11-56143727; API