11-124310573-C-A

Variant summary

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

The NM_001002917.2(OR8D1):​c.194G>T​(p.Ser65Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000039 ( 0 hom. )

Consequence

OR8D1
NM_001002917.2 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.76
Variant links:
Genes affected
OR8D1 (HGNC:8481): (olfactory receptor family 8 subfamily D 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=0.046616644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR8D1NM_001002917.2 linkuse as main transcriptc.194G>T p.Ser65Ile missense_variant 3/3 ENST00000641015.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR8D1ENST00000641015.1 linkuse as main transcriptc.194G>T p.Ser65Ile missense_variant 3/3 NM_001002917.2 P1
OR8D1ENST00000357821.2 linkuse as main transcriptc.194G>T p.Ser65Ile missense_variant 1/1 P1
OR8D1ENST00000641897.1 linkuse as main transcriptc.194G>T p.Ser65Ile missense_variant 4/4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152078
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000207
AC:
52
AN:
250726
Hom.:
0
AF XY:
0.000185
AC XY:
25
AN XY:
135486
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00148
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:
0.000164
GnomAD4 exome
AF:
0.0000390
AC:
57
AN:
1461676
Hom.:
0
Cov.:
33
AF XY:
0.0000385
AC XY:
28
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00125
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:
0.0000132
AC:
2
AN:
152078
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00
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
Bravo
AF:
0.000113
ExAC
AF:
0.0000906
AC:
11

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 GeneticsOct 12, 2021The c.194G>T (p.S65I) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a G to T substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 to be replaced by an isoleucine (I). 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
0.16
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
2.6
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0093
T;T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.041
.;.;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.98
L;L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-4.2
.;.;D
REVEL
Benign
0.069
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
0.86
P;P;P
Vest4
0.16
MutPred
0.49
Loss of catalytic residue at S65 (P = 0.0631);Loss of catalytic residue at S65 (P = 0.0631);Loss of catalytic residue at S65 (P = 0.0631);
MVP
0.33
MPC
0.044
ClinPred
0.24
T
GERP RS
-2.2
Varity_R
0.37
gMVP
0.39

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: rs772797738; hg19: chr11-124180469; API