Variant 11-124310012-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001002917.2(OR8D1):c.755T>C(p.Phe252Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,601,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

OR8D1
NM_001002917.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.849

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102210075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR8D1	NM_001002917.2 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	3/3	ENST00000641015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR8D1	ENST00000641015.1 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	3/3	NM_001002917.2	P1
OR8D1	ENST00000357821.2 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	1/1		P1
OR8D1	ENST00000641897.1 linkuse as main transcript	c.755T>C	p.Phe252Ser	missense_variant	4/4		P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000789

AC:

AN:

240670

Hom.:

AF XY:

0.0000923

AC XY:

AN XY:

129966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000827

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1449500

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

720182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.0000669

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000659

AC:

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 submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.755T>C (p.F252S) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a T to C substitution at nucleotide position 755, causing the phenylalanine (F) at amino acid position 252 to be replaced by a serine (S). 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

0.37

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.57

.;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-6.5

.;.;D

REVEL

Benign

0.11

Sift

Uncertain

0.0050

.;.;D

Sift4G

Uncertain

0.0060

.;.;D

Polyphen

0.96

D;D;D

Vest4

0.16

MutPred

0.54

Gain of glycosylation at F252 (P = 0.0438);Gain of glycosylation at F252 (P = 0.0438);Gain of glycosylation at F252 (P = 0.0438);

MVP

0.54

MPC

0.19

ClinPred

0.68

GERP RS

-0.23

Varity_R

0.55

gMVP

0.36

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