Variant 3-98169297-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001005515.2(OR5H15):c.598T>C(p.Phe200Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,610,988 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 54 hom. )

Consequence

OR5H15
NM_001005515.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.445

Variant links:

Genes affected

OR5H15 (HGNC:31287): (olfactory receptor family 5 subfamily H member 15) 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]

OR5H15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004107207).

BP6

Variant 3-98169297-T-C is Benign according to our data. Variant chr3-98169297-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2653998.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5H15	NM_001005515.2 linkuse as main transcript	c.598T>C	p.Phe200Leu	missense_variant	2/2	ENST00000641450.1	NP_001005515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5H15	ENST00000641450.1 linkuse as main transcript	c.598T>C	p.Phe200Leu	missense_variant	2/2		NM_001005515.2	ENSP00000493082	P1

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

887

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00834

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00636

AC:

1578

AN:

248006

Hom.:

AF XY:

0.00653

AC XY:

878

AN XY:

134394

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00450

Gnomad EAS exome

AF:

0.0000550

Gnomad SAS exome

AF:

0.000689

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.00904

Gnomad OTH exome

AF:

0.00781

GnomAD4 exome

AF:

0.00720

AC:

10498

AN:

1458800

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

4982

AN XY:

725858

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00529

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000709

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.00789

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00582

AC:

886

AN:

152188

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.00834

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00724

Hom.:

Bravo

AF:

0.00435

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00828

AC:

ExAC

AF:

0.00677

AC:

821

EpiCase

AF:

0.00557

EpiControl

AF:

0.00810

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

OR5H15: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

Polyphen

0.33

B;.

MutPred

0.46

Loss of glycosylation at S203 (P = 0.0281);Loss of glycosylation at S203 (P = 0.0281);

ClinPred

0.045

GERP RS

2.5

Varity_R

0.49

gMVP

0.092

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