Variant 11-58214950-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004458.4(OR1S1):c.167A>C(p.His56Pro) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR1S1
NM_001004458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.47

Variant links:

Genes affected

OR1S1 (HGNC:8227): (olfactory receptor family 1 subfamily S 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR1S1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1S1	NM_001004458.4 linkuse as main transcript	c.167A>C	p.His56Pro	missense_variant	2/2	ENST00000641544.1	NP_001004458.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1S1	ENST00000641544.1 linkuse as main transcript	c.167A>C	p.His56Pro	missense_variant	2/2		NM_001004458.4	ENSP00000493053	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151998

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000626

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00489

AC:

7055

AN:

1442612

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3268

AN XY:

718320

show subpopulations

Gnomad4 AFR exome

AF:

0.00368

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.000631

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00592

Gnomad4 OTH exome

AF:

0.00400

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000592

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.000626

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Nov 21, 2022

The c.206A>C (p.H69P) alteration is located in exon 1 (coding exon 1) of the OR1S1 gene. This alteration results from a A to C substitution at nucleotide position 206, causing the histidine (H) at amino acid position 69 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0082

.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0029

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

4.5

.;H

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

Polyphen

1.0

.;D

MutPred

0.61

.;Gain of glycosylation at H69 (P = 0.074);

ClinPred

1.0

GERP RS

3.5

Varity_R

0.92

gMVP

0.26

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