Genetic Variant OR8D1:p.Pro58Leu (chr11-124310594-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001002917.2(OR8D1):c.173C>T(p.Pro58Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

OR8D1
NM_001002917.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

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]

OR8D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8D1	NM_001002917.2 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 3 of 3	ENST00000641015.1	NP_001002917.1	Q8WZ84A0A126GVG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR8D1	ENST00000641015.1 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 3 of 3		NM_001002917.2	ENSP00000493365.1	Q8WZ84
OR8D1	ENST00000357821.2 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 1 of 1	6		ENSP00000350474.2	Q8WZ84
OR8D1	ENST00000641897.1 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 4 of 4			ENSP00000493091.1	Q8WZ84

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250902

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135588

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173C>T (p.P58L) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the proline (P) at amino acid position 58 to be replaced by a leucine (L). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.9

H;H;H

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-8.8

.;.;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.73

MutPred

0.62

Gain of catalytic residue at P58 (P = 0.0885);Gain of catalytic residue at P58 (P = 0.0885);Gain of catalytic residue at P58 (P = 0.0885);

MVP

0.35

MPC

0.17

ClinPred

1.0

GERP RS

2.4

Varity_R

0.74

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over