Variant 3-98264441-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005479.2(OR5H6):c.109A>C(p.Ile37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR5H6
NM_001005479.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.79

Variant links:

Genes affected

OR5H6 (HGNC:14767): (olfactory receptor family 5 subfamily H member 6) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR5H6 links:

ENSG00000251088 (HGNC:):

ENSG00000251088 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05639693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5H6	NM_001005479.2 linkuse as main transcript	c.109A>C	p.Ile37Leu	missense_variant	1/1	ENST00000615035.3	NP_001005479.2	Q8NGV6A0A126GW86
LOC105373999	XR_001740814.2 linkuse as main transcript	n.536-1299T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5H6	ENST00000615035.3 linkuse as main transcript	c.109A>C	p.Ile37Leu	missense_variant	1/1	6	NM_001005479.2	ENSP00000480705.3		A0A126GW86

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151934

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00410

AC:

5682

AN:

1384326

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

2540

AN XY:

691466

show subpopulations

Gnomad4 AFR exome

AF:

0.00581

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.000609

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00494

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000132

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 29, 2023

The c.157A>C (p.I53L) alteration is located in exon 1 (coding exon 1) of the OR5H6 gene. This alteration results from a A to C substitution at nucleotide position 157, causing the isoleucine (I) at amino acid position 53 to be replaced by a leucine (L). 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

0.067

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.0

DANN

Benign

0.88

DEOGEN2

Benign

0.0067

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.00074

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.58

.;.;N

PrimateAI

Benign

0.29

Polyphen

0.020

.;.;B

MutPred

0.30

.;.;Loss of glycosylation at T54 (P = 0.1655);

ClinPred

0.056

GERP RS

-1.1

Varity_R

0.13

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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