Variant chr17-3092830-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_002548.3(OR1D2):c.167A>C(p.His56Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR1D2
NM_002548.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

OR1D2 (HGNC:8183): (olfactory receptor family 1 subfamily D member 2) 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]

OR1D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1D2	NM_002548.3 link	c.167A>C	p.His56Pro	missense_variant	2/2	ENST00000641833.1	NP_002539.2	P34982A0A126GVV4
OR1D2	NM_001386088.1 link	c.167A>C	p.His56Pro	missense_variant	2/2		NP_001373017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1D2	ENST00000641833.1 link	c.167A>C	p.His56Pro	missense_variant	2/2		NM_002548.3	ENSP00000493103.1		P34982
OR1D2	ENST00000641064.1 link	c.167A>C	p.His56Pro	missense_variant	2/2			ENSP00000493077.1		P34982

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151862

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00247

AC:

3588

AN:

1455244

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1647

AN XY:

724038

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.000759

Gnomad4 SAS exome

AF:

0.000882

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00294

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000921

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2023

The c.167A>C (p.H56P) alteration is located in exon 1 (coding exon 1) of the OR1D2 gene. This alteration results from a A to C substitution at nucleotide position 167, causing the histidine (H) at amino acid position 56 to be replaced by a proline (P). 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

0.21

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;.;T

M_CAP

Benign

0.0024

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.9

H;H;H

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-7.3

.;.;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.59

MutPred

0.77

Gain of glycosylation at H56 (P = 0.134);Gain of glycosylation at H56 (P = 0.134);Gain of glycosylation at H56 (P = 0.134);

MVP

0.75

MPC

0.54

ClinPred

1.0

GERP RS

3.0

Varity_R

0.92

gMVP

0.67

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