11-56105590-C-A

Position:

chr11-56105590-C-A

Variant summary

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

The NM_001386064.1(OR8H2):c.548C>A(p.Pro183Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

OR8H2
NM_001386064.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

OR8H2 (HGNC:15308): (olfactory receptor family 8 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]

OR8H2 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=0.107757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8H2	NM_001386064.1 linkuse as main transcript	c.548C>A	p.Pro183Gln	missense_variant	2/2	ENST00000313503.2	NP_001372993.1
OR8H2	NM_001005200.2 linkuse as main transcript	c.548C>A	p.Pro183Gln	missense_variant	2/2		NP_001005200.1	Q8N162

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR8H2	ENST00000313503.2 linkuse as main transcript	c.548C>A	p.Pro183Gln	missense_variant	2/2	6	NM_001386064.1	ENSP00000323982.1	Q8N162
OR8H2	ENST00000641311.1 linkuse as main transcript	c.548C>A	p.Pro183Gln	missense_variant	2/2			ENSP00000493031.1	Q8N162
OR8H2	ENST00000618136.1 linkuse as main transcript	c.545C>A	p.Pro182Gln	missense_variant	1/1	6		ENSP00000482661.1	A0A087WZH1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251348

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000369

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000289

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Jul 02, 2024

The c.548C>A (p.P183Q) alteration is located in exon 1 (coding exon 1) of the OR8H2 gene. This alteration results from a C to A substitution at nucleotide position 548, causing the proline (P) at amino acid position 183 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

0.21

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0055

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.5

L;L;.

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-6.9

D;.;.

REVEL

Benign

0.037

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;D;.

Vest4

0.19

MVP

0.39

MPC

0.53

ClinPred

0.43

GERP RS

2.7

Varity_R

0.58

gMVP

0.095

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