Variant 1-248099736-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395936.1(OR2L13):c.361C>T(p.Arg121Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OR2L13
NM_001395936.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.144

Variant links:

Genes affected

OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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]

OR2L13 links:

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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	Protein	UniProt
OR2L13	NM_001395936.1 link	c.361C>T	p.Arg121Cys	missense_variant	3/3	ENST00000358120.4	NP_001382865.1
OR2L13	NM_001304535.3 link	c.361C>T	p.Arg121Cys	missense_variant	2/2		NP_001291464.1	Q8N349A0A126GW96
OR2L13	NM_175911.5 link	c.361C>T	p.Arg121Cys	missense_variant	3/3		NP_787107.1	Q8N349A0A126GW96
OR2L13	XM_011544169.3 link	c.361C>T	p.Arg121Cys	missense_variant	3/3		XP_011542471.1	Q8N349A0A126GW96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2L13	ENST00000358120.4 link	c.361C>T	p.Arg121Cys	missense_variant	3/3	6	NM_001395936.1	ENSP00000350836.2	Q8N349
OR2L13	ENST00000641714.1 link	c.361C>T	p.Arg121Cys	missense_variant	3/3			ENSP00000493075.1	Q8N349
OR2L13	ENST00000641893.1 link	c.361C>T	p.Arg121Cys	missense_variant	2/2			ENSP00000492949.1	Q8N349

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251430

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000611

Hom.:

ExAC

AF:

0.0000330

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

Feb 05, 2024

The c.361C>T (p.R121C) alteration is located in exon 3 (coding exon 1) of the OR2L13 gene. This alteration results from a C to T substitution at nucleotide position 361, causing the arginine (R) at amino acid position 121 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.94

.;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.20

PROVEAN

Pathogenic

-7.0

D;.;.

REVEL

Uncertain

0.44

Sift

Uncertain

0.015

D;.;.

Sift4G

Uncertain

0.017

D;.;.

Polyphen

1.0

D;D;D

Vest4

0.12

MVP

0.82

ClinPred

0.78

GERP RS

2.2

Varity_R

0.42

gMVP

0.72

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