11-124310328-C-T

Variant summary

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

The NM_001002917.2(OR8D1):​c.439G>A​(p.Ala147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

OR8D1
NM_001002917.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.441
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=0.06613481).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR8D1NM_001002917.2 linkc.439G>A p.Ala147Thr missense_variant Exon 3 of 3 ENST00000641015.1 NP_001002917.1 Q8WZ84A0A126GVG6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR8D1ENST00000641015.1 linkc.439G>A p.Ala147Thr missense_variant Exon 3 of 3 NM_001002917.2 ENSP00000493365.1 Q8WZ84
OR8D1ENST00000357821.2 linkc.439G>A p.Ala147Thr missense_variant Exon 1 of 1 6 ENSP00000350474.2 Q8WZ84
OR8D1ENST00000641897.1 linkc.439G>A p.Ala147Thr missense_variant Exon 4 of 4 ENSP00000493091.1 Q8WZ84

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000639
AC:
16
AN:
250326
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135274
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:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000411
AC:
60
AN:
1461466
Hom.:
0
Cov.:
37
AF XY:
0.0000358
AC XY:
26
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
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:
0.0000477
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000119
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.439G>A (p.A147T) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a G to A substitution at nucleotide position 439, causing the alanine (A) at amino acid position 147 to be replaced by a threonine (T). 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
0.084
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
7.4
DANN
Benign
0.93
DEOGEN2
Benign
0.0097
T;T;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.13
.;.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.066
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.82
L;L;L
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.6
.;.;N
REVEL
Benign
0.029
Sift
Benign
0.11
.;.;T
Sift4G
Uncertain
0.030
.;.;D
Polyphen
0.15
B;B;B
Vest4
0.085
MVP
0.26
MPC
0.025
ClinPred
0.064
T
GERP RS
-0.026
Varity_R
0.084
gMVP
0.057

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs370123664; hg19: chr11-124180224; COSMIC: COSV100766576; API