Variant 19-9185948-A-C 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_175883.4(OR7D2):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 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR7D2
NM_175883.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

OR7D2 (HGNC:8378): (olfactory receptor family 7 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]

OR7D2 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, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR7D2	NM_175883.4 link	c.167A>C	p.His56Pro	missense_variant	3/3	ENST00000641288.2	NP_787079.1	Q96RA2
OR7D2	NM_001386112.1 link	c.167A>C	p.His56Pro	missense_variant	2/2		NP_001373041.1
OR7D2	XM_047438317.1 link	c.167A>C	p.His56Pro	missense_variant	2/2		XP_047294273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR7D2	ENST00000641288.2 link	c.167A>C	p.His56Pro	missense_variant	3/3		NM_175883.4	ENSP00000493200.1	Q96RA2
OR7D2	ENST00000344248.4 link	c.167A>C	p.His56Pro	missense_variant	1/1	6		ENSP00000345563.2	Q96RA2
OR7D2	ENST00000642043.1 link	c.167A>C	p.His56Pro	missense_variant	2/2			ENSP00000492939.1	Q96RA2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151864

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00248

AC:

3599

AN:

1452106

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1683

AN XY:

722666

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.000582

Gnomad4 SAS exome

AF:

0.000767

Gnomad4 FIN exome

AF:

0.000263

Gnomad4 NFE exome

AF:

0.00296

Gnomad4 OTH exome

AF:

0.00213

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000592

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.0000294

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

Apr 08, 2024

The c.167A>C (p.H56P) alteration is located in exon 1 (coding exon 1) of the OR7D2 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

0.28

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;T;T

Eigen

Uncertain

0.43

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.46

.;.;T

M_CAP

Benign

0.0014

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Pathogenic

4.4

H;H;H

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-8.0

.;.;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.54

MutPred

0.77

Gain of glycosylation at T57 (P = 0.0582);Gain of glycosylation at T57 (P = 0.0582);Gain of glycosylation at T57 (P = 0.0582);

MVP

0.54

MPC

0.50

ClinPred

1.0

GERP RS

2.2

Varity_R

0.96

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