Variant 3-98132865-T-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_001005338.2(OR5H1):c.168T>G(p.His56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,607,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

OR5H1
NM_001005338.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00300

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:

(HGNC:):

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=0.074601054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5H1	NM_001005338.2 linkuse as main transcript	c.168T>G	p.His56Gln	missense_variant	2/2	ENST00000641874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5H1	ENST00000641874.1 linkuse as main transcript	c.168T>G	p.His56Gln	missense_variant	2/2		NM_001005338.2	P1
	ENST00000508964.1 linkuse as main transcript	n.94+15176A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

147028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000678

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000294

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000136

Gnomad OTH

AF:

0.000497

GnomAD3 exomes

AF:

0.0000924

AC:

AN:

249002

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1460474

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000211

AC:

AN:

147136

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

AN XY:

71856

show subpopulations

Gnomad4 AFR

AF:

0.000202

Gnomad4 AMR

AF:

0.000677

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000294

Gnomad4 NFE

AF:

0.000136

Gnomad4 OTH

AF:

0.000491

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.000107

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

Mar 07, 2024

The c.168T>G (p.H56Q) alteration is located in exon 1 (coding exon 1) of the OR5H1 gene. This alteration results from a T to G substitution at nucleotide position 168, causing the histidine (H) at amino acid position 56 to be replaced by a glutamine (Q). 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

0.29

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0085

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-7.0

.;D

REVEL

Benign

0.042

Sift

Benign

0.053

.;T

Sift4G

Uncertain

0.059

.;T

Polyphen

0.49

P;P

Vest4

0.35

MutPred

0.52

Gain of catalytic residue at H56 (P = 0.0511);Gain of catalytic residue at H56 (P = 0.0511);

MVP

0.27

MPC

0.49

ClinPred

0.071

GERP RS

0.60

Varity_R

0.43

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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