Variant 11-5986020-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001005173.3(OR52L1):c.911C>T(p.Ala304Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

OR52L1
NM_001005173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.928

Variant links:

Genes affected

OR52L1 (HGNC:14785): (olfactory receptor family 52 subfamily L 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]

OR52L1 links:

OR56A3 (HGNC:):

OR56A3 links:

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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=0.085879356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52L1	NM_001005173.3 linkuse as main transcript	c.911C>T	p.Ala304Val	missense_variant	1/1	ENST00000332249.4
OR56A3	XM_047426926.1 linkuse as main transcript	c.*469-17700G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52L1	ENST00000332249.4 linkuse as main transcript	c.911C>T	p.Ala304Val	missense_variant	1/1		NM_001005173.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000137

AC:

AN:

247608

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134386

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1460880

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000151

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.000355

AC:

ExAC

AF:

0.000165

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

May 27, 2022

The c.911C>T (p.A304V) alteration is located in exon 1 (coding exon 1) of the OR52L1 gene. This alteration results from a C to T substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.017

M_CAP

Benign

0.0031

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.17

PROVEAN

Benign

0.62

REVEL

Benign

0.15

Sift

Benign

0.37

Sift4G

Benign

0.41

Vest4

0.047

MVP

0.41

MPC

0.14

ClinPred

0.048

GERP RS

2.7

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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