3-98283237-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005482.2(OR5H2):c.335G>A(p.Cys112Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

OR5H2
NM_001005482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.190

Variant links:

Genes affected

OR5H2 (HGNC:14752): (olfactory receptor family 5 subfamily H 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]

OR5H2 links:

ENSG00000251088 (HGNC:):

ENSG00000251088 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=0.22327453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5H2	NM_001005482.2 link	c.335G>A	p.Cys112Tyr	missense_variant	Exon 1 of 1	ENST00000355273.3	NP_001005482.2	Q8NGV7
LOC105373999	XR_001740814.2 link	n.71-3349C>T		intron_variant	Intron 1 of 3
LOC105373999	XR_924258.2 link	n.216-5762C>T		intron_variant	Intron 1 of 2
LOC105373999	XR_924259.2 link	n.71-3349C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5H2	ENST00000355273.3 link	c.335G>A	p.Cys112Tyr	missense_variant	Exon 1 of 1	6	NM_001005482.2	ENSP00000347418.3		Q8NGV7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250958

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350G>A (p.C117Y) alteration is located in exon 1 (coding exon 1) of the OR5H2 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the cysteine (C) at amino acid position 117 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

-0.096

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-10

D;D

REVEL

Benign

0.070

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.021

D;.

Polyphen

1.0

D;.

Vest4

0.31

MVP

0.64

MPC

0.030

ClinPred

0.99

GERP RS

2.3

Varity_R

0.92

gMVP

0.37

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