Variant 19-9251264-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001079935.2(OR7E24):c.221A>C(p.His74Pro) 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR7E24
NM_001079935.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

OR7E24 (HGNC:8396): (olfactory receptor family 7 subfamily E member 24) 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]

OR7E24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR7E24	NM_001079935.2 link	c.221A>C	p.His74Pro	missense_variant	Exon 1 of 1	ENST00000456448.3	NP_001073404.1	Q6IFN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR7E24	ENST00000456448.3 link	c.221A>C	p.His74Pro	missense_variant	Exon 1 of 1	6	NM_001079935.2	ENSP00000387523.1		Q6IFN5
OR7E24	ENST00000641946.1 link	c.209A>C	p.His70Pro	missense_variant	Exon 2 of 2			ENSP00000494223.1		A0A2R8Y4Q1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151734

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000969

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00319

AC:

4633

AN:

1450218

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

2209

AN XY:

721898

show subpopulations

Gnomad4 AFR exome

AF:

0.00256

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.000961

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.000319

Gnomad4 NFE exome

AF:

0.00380

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000138

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000971

Gnomad4 SAS

AF:

0.000627

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000118

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

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.221A>C (p.H74P) alteration is located in exon 1 (coding exon 1) of the OR7E24 gene. This alteration results from a A to C substitution at nucleotide position 221, causing the histidine (H) at amino acid position 74 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

0.25

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0018

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

4.0

.;H

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-8.5

.;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.16

.;B

Vest4

0.51

MutPred

0.74

.;Gain of glycosylation at T75 (P = 0.068);

MVP

0.33

MPC

0.021

ClinPred

0.99

GERP RS

2.4

Varity_R

0.93

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