Variant 11-58267500-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207374.3(OR10W1):c.359C>T(p.Pro120Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

OR10W1
NM_207374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.05

Variant links:

Genes affected

OR10W1 (HGNC:15139): (olfactory receptor family 10 subfamily W member 1) 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]

OR10W1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10W1	NM_207374.3 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	1/1	ENST00000395079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10W1	ENST00000395079.2 linkuse as main transcript	c.359C>T	p.Pro120Leu	missense_variant	1/1		NM_207374.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250702

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000204

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000433

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Aug 02, 2023

The c.359C>T (p.P120L) alteration is located in exon 1 (coding exon 1) of the OR10W1 gene. This alteration results from a C to T substitution at nucleotide position 359, causing the proline (P) at amino acid position 120 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

0.23

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.84

MVP

0.39

MPC

0.27

ClinPred

0.99

GERP RS

4.9

Varity_R

0.79

gMVP

0.54

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