Variant 3-98133390-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005338.2(OR5H1):c.693T>A(p.Asp231Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,613,160 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

OR5H1
NM_001005338.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.51

Variant links:

Genes affected

OR5H1 (HGNC:8346): (olfactory receptor family 5 subfamily H 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]

OR5H1 links:

ENSG00000249225 (HGNC:):

ENSG00000249225 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009464383).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5H1	NM_001005338.2 linkuse as main transcript	c.693T>A	p.Asp231Glu	missense_variant	2/2	ENST00000641874.1	NP_001005338.1	A6NKK0A0A126GW79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5H1	ENST00000641874.1 linkuse as main transcript	c.693T>A	p.Asp231Glu	missense_variant	2/2		NM_001005338.2	ENSP00000492953.1		A6NKK0
ENSG00000249225	ENST00000508964.1 linkuse as main transcript	n.94+14651A>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000677

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000395

AC:

AN:

250902

Hom.:

AF XY:

0.000450

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000520

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000435

AC:

635

AN:

1461060

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

317

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000447

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000375

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000677

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000365

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000519

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 01, 2021

The c.693T>A (p.D231E) alteration is located in exon 1 (coding exon 1) of the OR5H1 gene. This alteration results from a T to A substitution at nucleotide position 693, causing the aspartic acid (D) at amino acid position 231 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.35

DEOGEN2

Benign

0.0012

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.069

.;T

M_CAP

Benign

0.00043

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.79

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

1.3

.;N

REVEL

Benign

0.036

Sift

Benign

0.94

.;T

Sift4G

Benign

0.59

.;T

Polyphen

0.0

B;B

Vest4

0.042

MutPred

0.33

Gain of methylation at K229 (P = 0.0708);Gain of methylation at K229 (P = 0.0708);

MVP

0.076

MPC

0.23

ClinPred

0.023

GERP RS

-7.1

Varity_R

0.029

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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