Variant 19-15794447-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004466.2(OR10H5):c.399C>A(p.Asn133Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,152 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 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

OR10H5
NM_001004466.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -8.66

Variant links:

Genes affected

OR10H5 (HGNC:15389): (olfactory receptor family 10 subfamily H member 5) 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]

OR10H5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027299255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10H5	NM_001004466.2 linkuse as main transcript	c.399C>A	p.Asn133Lys	missense_variant	2/2	ENST00000642092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10H5	ENST00000642092.2 linkuse as main transcript	c.399C>A	p.Asn133Lys	missense_variant	2/2		NM_001004466.2	P1
OR10H5	ENST00000308940.8 linkuse as main transcript	c.399C>A	p.Asn133Lys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000747

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000716

AC:

AN:

251394

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.0000578

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:

0.0000315

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000134

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:

0.000149

GnomAD4 genome

AF:

0.000217

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.000131

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

Bravo

AF:

0.000344

ExAC

AF:

0.0000576

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

Apr 17, 2024

The c.399C>A (p.N133K) alteration is located in exon 1 (coding exon 1) of the OR10H5 gene. This alteration results from a C to A substitution at nucleotide position 399, causing the asparagine (N) at amino acid position 133 to be replaced by a lysine (K). 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

0.18

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.060

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0010

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.092

.;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.39

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.72

.;N

REVEL

Benign

0.11

Sift

Benign

0.085

.;T

Sift4G

Uncertain

0.041

.;D

Polyphen

0.90

P;P

Vest4

0.10

MutPred

0.51

Gain of methylation at N133 (P = 0.0287);Gain of methylation at N133 (P = 0.0287);

MVP

0.23

MPC

0.35

ClinPred

0.11

GERP RS

-5.9

Varity_R

0.16

gMVP

0.049

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