Variant 10-45303754-G-T 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_001004297.3(OR13A1):c.669C>A(p.Phe223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

OR13A1
NM_001004297.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

OR13A1 (HGNC:14772): (olfactory receptor family 13 subfamily A 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]

OR13A1 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=0.047733277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR13A1	NM_001004297.3 link	c.669C>A	p.Phe223Leu	missense_variant	4/4	ENST00000553795.6	NP_001004297.2	Q8NGR1A0A126GVD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR13A1	ENST00000553795.6 link	c.669C>A	p.Phe223Leu	missense_variant	4/4	6	NM_001004297.3	ENSP00000451950.1	Q8NGR1
OR13A1	ENST00000374401.3 link	c.669C>A	p.Phe223Leu	missense_variant	4/4	6		ENSP00000363522.2	Q8NGR1
OR13A1	ENST00000536058.1 link	c.669C>A	p.Phe223Leu	missense_variant	3/3	6		ENSP00000438657.1	Q8NGR1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251260

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000347

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:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

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:

0.000163

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000197

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000110

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 02, 2024

The c.669C>A (p.F223L) alteration is located in exon 4 (coding exon 1) of the OR13A1 gene. This alteration results from a C to A substitution at nucleotide position 669, causing the phenylalanine (F) at amino acid position 223 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.5

DANN

Benign

0.78

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.078

M_CAP

Benign

0.0057

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.68

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.060

B;B;B

Vest4

0.14

MutPred

0.66

Loss of catalytic residue at F223 (P = 0.0354);Loss of catalytic residue at F223 (P = 0.0354);Loss of catalytic residue at F223 (P = 0.0354);

MVP

0.040

MPC

0.028

ClinPred

0.094

GERP RS

-6.1

Varity_R

0.14

gMVP

0.077

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